CN108410986A - CDH6 promotes Growth of Osteosarcoma and transfer - Google Patents
CDH6 promotes Growth of Osteosarcoma and transfer Download PDFInfo
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- CN108410986A CN108410986A CN201810162051.2A CN201810162051A CN108410986A CN 108410986 A CN108410986 A CN 108410986A CN 201810162051 A CN201810162051 A CN 201810162051A CN 108410986 A CN108410986 A CN 108410986A
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- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
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Abstract
The invention discloses CDH6 to promote Growth of Osteosarcoma and transfer.The present invention provides CDH6 albumen and for promote the substance that it is expressed it is following it is any in application：It prepares for promoting osteosarcoma cell invasion, migration and/or the product of proliferation；Or product of the preparation for promoting Growth of Osteosarcoma and/or transfer.It is demonstrated experimentally that CDH6 and Patients with Osteosarcoma overall survival and prognosis are closely related.The present invention also found that CDH6 is overexpressed the invasion, migration and proliferation that can promote osteosarcoma cell by experiment.Therefore, CDH6 is likely to become the new biomarker and therapeutic targets for the treatment of prognosis in osteosarcoma.
Description
Technical field
The invention belongs to biotechnologies, are related to CDH6 and Growth of Osteosarcoma and transfer, more particularly to CDH6 is promoted to make
It is ready for use on answering in the product (such as cell model or animal model of osteosarcoma generation/development) for promoting Growth of Osteosarcoma and transfer
With, and application of the substance that CDH6 is expressed in preparing the product for inhibiting Growth of Osteosarcoma and transfer can be inhibited.
Background technology
Osteosarcoma is used as current most common bone malignant change, worldwide incidence in Children and teenager crowd
It is high.Currently, after DISTANT METASTASES IN occurs for Patients with Osteosarcoma, survival rate is down to 10%-30%.Nearest bioinformatics and other sections
The progress of technology has discovered that the potential method of some treatment osteosarcoma.However, the clinical therapeutic efficacy of Patients with Osteosarcoma
But it is not obviously improved.Therefore, it finds better osteosarcoma clinical treatment and understands mechanism of action therein to pass
It is important.
Integrin 6 (CDH6) as important regulatory factor, kidney and peripheral nervous system development and disease into
Key effect is played in exhibition.But the effect in osteosarcoma occurrence and development is still unknown.
Invention content
The object of the present invention is to provide CDH6 albumen and its new applications of relevant biological material.
In a first aspect, any one of substance shown in claimed following (1)-(3) following (a)-(e) at least
A kind of application in：
(1) CDH6 albumen；
(2) nucleic acid molecules of CDH6 albumen are encoded；
(3) contain expression cassette, recombinant vector or the transgenic cell of the nucleic acid molecules；
(a) promote osteosarcoma cell invasion, or prepare the product for promoting osteosarcoma cell to invade；
(b) promote osteosarcoma cell migration, or prepare the product for promoting osteosarcoma cell to migrate；
(c) promote human osteosarcoma cell proliferation, or prepare the product for promoting human osteosarcoma cell proliferation；
(d) promote Growth of Osteosarcoma, or prepare the product for promoting Growth of Osteosarcoma；
(e) promote bone and flesh tumor metastasis, or prepare the product for promoting bone and flesh tumor metastasis.
Second aspect, the claimed substance that following (1) or (2) expression and/or activity can be promoted to improve exist
Application during (a)-(e) is at least one as follows：
(1) CDH6 albumen；
(2) nucleic acid molecules of CDH6 albumen are encoded；
(a) promote osteosarcoma cell invasion, or prepare the product for promoting osteosarcoma cell to invade；
(b) promote osteosarcoma cell migration, or prepare the product for promoting osteosarcoma cell to migrate；
(c) promote human osteosarcoma cell proliferation, or prepare the product for promoting human osteosarcoma cell proliferation；
(d) promote Growth of Osteosarcoma, or prepare the product for promoting Growth of Osteosarcoma；
(e) promote bone and flesh tumor metastasis, or prepare the product for promoting bone and flesh tumor metastasis.
In application described in above-mentioned first aspect and second aspect, the product for promoting osteosarcoma cell to invade
It can be the osteosarcoma cell model of invasive ability enhancing, or be used to prepare the osteosarcoma cell model of invasive ability enhancing
Substance.
In application described in above-mentioned first aspect and second aspect, the product for promoting osteosarcoma cell to migrate
It can be the osteosarcoma cell model of transfer ability enhancing, or be used to prepare the osteosarcoma cell model of transfer ability enhancing
Substance.
In application described in above-mentioned first aspect and second aspect, the product for promoting human osteosarcoma cell proliferation
It can be the osteosarcoma cell model of proliferative capacity enhancing, or be used to prepare the osteosarcoma cell model of proliferative capacity enhancing
Substance.
In application described in above-mentioned first aspect and second aspect, the product for promoting Growth of Osteosarcoma
For Growth of Osteosarcoma ability enhancing animal model, or be used to prepare Growth of Osteosarcoma ability enhancing animal model object
Matter.
In application described in above-mentioned first aspect and second aspect, the product for promoting bone and flesh tumor metastasis
For osteosarcoma transfer ability enhancing animal model, or be used to prepare osteosarcoma transfer ability enhancing animal model object
Matter.
The third aspect, the claimed substance that following (1) or (2) expression and/or activity can be inhibited to reduce exist
Application during (a ')-(e ') is at least one as follows：
(1) CDH6 albumen；
(2) nucleic acid molecules of CDH6 albumen are encoded；
(a ') inhibits osteosarcoma cell invasion, or prepares the product for inhibiting osteosarcoma cell to invade；
(b ') inhibits osteosarcoma cell migration, or prepares the product for inhibiting osteosarcoma cell to migrate；
(c ') inhibits human osteosarcoma cell proliferation, or prepares the product for inhibiting human osteosarcoma cell proliferation；
(d ') inhibits Growth of Osteosarcoma, or prepares the product for inhibiting Growth of Osteosarcoma；
(e ') inhibits bone and flesh tumor metastasis, or prepares the product for inhibiting bone and flesh tumor metastasis.
In the application, the product can be drug or health products etc..
Fourth aspect, any one of substance shown in claimed following (1)-(2) as treat and/
Or the application in the target of prevention osteosarcoma：
(1) CDH6 albumen；
(2) nucleic acid molecules of CDH6 albumen are encoded.
In application described in above-mentioned first, second, third and fourth aspect, the CDH6 albumen concretely people source
CDH6 albumen.
Further, the CDH6 albumen is concretely following any：
(A1) amino acid sequence is the protein of SEQ ID No.1；
(A2) by amino acid sequence shown in SEQ ID No.1 by one or several amino acid residues substitution and/or
It lacks and ors add and protein with the same function；
(A3) with (A1)-(A2) in it is any defined by amino acid sequence have 99% or more, 95% or more, 90% with
Upper, 85% or more or 80% or more homology and protein with the same function；
(A4) fusion obtained after the N-terminal of protein defined by any in (A1)-(A3) and/or C-terminal connection label
Albumen.
Correspondingly, the nucleic acid molecules of the coding CDH6 albumen are specially following any DNA molecular：
(a1) DNA molecular shown in SEQ ID No.2；
(a2) hybridize under strict conditions with (a1) DNA molecular limited and encode the DNA molecular of the CDH6 albumen；
(a3) have 99% or more, 95% or more, 90% or more, 85% with the DNA sequence dna of any restriction in (a1)-(a2)
Above or the DNA molecular of 80% or more homology and the coding CDH6 albumen.
Above-mentioned stringent condition can be with 6 × SSC, and the solution of 0.5%SDS hybridizes at 65 DEG C, then with 2 × SSC,
It is primary that 0.1%SDS and 1 × SSC, 0.1%SDS respectively wash film.
Correspondingly, in the present invention, " recombinant vector containing the nucleic acid molecules " is specially pcDNA3-FLAG-
CDH6 (replaces with the small fragment between the restriction enzyme site KpnI and XhoI of pcDNA3-FLAG carriers shown in SEQ ID No.2
Recombinant plasmid after DNA fragmentation).
Further, in the application described in above-mentioned first, second, third and fourth aspect, the osteosarcoma cell tool
Body is osteosarcoma cell line 143B.
It is demonstrated experimentally that CDH6 and Patients with Osteosarcoma overall survival and prognosis are closely related.The present invention by experiment it has also been found that,
CDH6 is overexpressed the invasion, migration and proliferation that can promote osteosarcoma cell.Therefore, it is pre- to be likely to become treatment osteosarcoma by CDH6
New biomarker and therapeutic targets afterwards.
Description of the drawings
Fig. 1 is that CDH6 is overexpressed the invasion characteristic expressed and can promote osteosarcoma cell line.
Fig. 2 is that CDH6 is overexpressed the migration that can remarkably promote osteosarcoma cell line.
Fig. 3 is the clonality that CDH6 can remarkably promote osteosarcoma cell line.
Fig. 4 is that CDH6 and Patients with Osteosarcoma clinical prognosis are closely related.A is histopathological analysis Patients with Osteosarcoma bone and flesh
The expression of CDH6 in tumor tissue and cancer beside organism.B, which is CDH6 scorings, proves that compared with cancerous issue, CDH6 is in bone and flesh
Significantly up-regulation is expressed in tumor tissue.C proves that CDH6 expresses notable up-regulation in osteosarcoma tissue for qRT-PCR.D is Kaplan
Meier survival analysis shows that the patient that CDH6 expressions are low in Patients with Osteosarcoma has relative to the patient of high expression CDH6
Preferable DFS phase (p=0.024).E is that Kaplan Meier survival analysis shows that CDH6 expresses water in Patients with Osteosarcoma
Flat low patient has preferable overall survival (p=0.018) relative to the patient of high expression CDH6.
Specific implementation mode
Experimental method used in following embodiments is conventional method unless otherwise specified.
The materials, reagents and the like used in the following examples is commercially available unless otherwise specified.
Involved CDH6 albumen behaviours source CDH6 albumen in following embodiments, amino acid sequence is specially SEQ ID
No.1, corresponding gene order are specially SEQ ID No.2.
In following embodiments, survival analysis uses Kaplan Meier methods, the difference Log-Rank Test of survivorship curve into
Row assessment.Single factor test and multiplicity are carried out using Cox regression models.Quantitative data is merged into using one-way analysis of variance
Performing check is assessed.Pearson χ are passed through using 6 softwares of GraphPad Prism2Carry out correlation analysis.Statistics, which calculates, to be used
17.0 softwares of SPSS carry out.All experiment in vitro are repeated three times above.Data are indicated with means standard deviation (SD).p<
0.05 is considered to have statistical significance.
Embodiment 1, CDH6 promote Growth of Osteosarcoma and transfer
One, CDH6 is overexpressed the preparation of osteosarcoma cell line
1, the structure of CDH6 over-express vectors pcDNA3-FLAG-CDH6
Routinely PCR method, using target gene CDH6 is template shown in SEQ ID No.2, using primer upstream 5 '-GGTACCATGAGAACTTACCGCTACTTCTT-3 ', downstream 5 '-CTCGAGTTAGGAGTCT TTGTCACTGTCCA-3 ' into
Row PCR amplification, KpnI and XhoI double digestions PCR product and respective carrier pcDNA3-FLAG (Invitrogen Products, goods
Number for 20011), by correct phase by purpose segment insertion carrier.Inverted, screening obtains positive colony digestion identification, analysis
The expression of various recombinant proteins, all recombinant plasmids send Beijing Bo Maide Bioisystech Co., Ltd to be sequenced.It will show after sequencing
Small fragment between the restriction enzyme site KpnI and XhoI of pcDNA3-FLAG carriers is replaced with into DNA fragmentation shown in SEQ ID No.2
Recombinant plasmid afterwards is named as pcDNA3-FLAG-CDH6.
2, CDH6 is overexpressed the preparation of osteosarcoma cell line
To 143B cells (American Type Culture Collection,CRL8303TM) in be transferred to weight
After group carrier pcDNA3-FLAG-CDH6 stably transfected cell line stable clone osteosarcoma 143B cell lines are obtained through pressure system.
Two, scratch experiment
For trying cell：CDH6 prepared by step 1 is overexpressed osteosarcoma cell line；And as a contrast to 143B cells
In be transferred to the unloaded control cells of pcDNA3-FLAG empty carriers.
Marker are first used to be compared with ruler in 6 orifice plates behind, it is uniform to draw horizontal line, together per every about 0.5-1cm,
Cross via.Per hole at least across 5 lines.Secondly about 5 × 10 are added in hole5A cell, particular number is due to cell difference
Difference is grasped as that can be paved with overnight.Compare ruler with pipette tips within second day, as possible perpendicular to the horizontal line cut of behind, pipette tips will hang down
Directly, it cannot tilt.Then cell is washed 3 times with PBS, serum free medium is added in the cell under place to go stroke.It is put into 37 DEG C of 5%CO2
Incubator, culture.It sampled, takes pictures by 0,6,12,24 hour.
Three, cell invasion is tested
For trying cell：CDH6 prepared by step 1 is overexpressed osteosarcoma cell line；And as a contrast to 143B cells
In be transferred to the unloaded control cells of pcDNA3-FLAG empty carriers.
The tumour cell of logarithmic growth phase, with 0.1% bovine serum albumin (BSA) DMEM culture solutions adjustment cell number for 1
×106cells/ml.Take 100 μ l cell inoculations in indoor on transwell, the isometric serum-free DMEM cultures of control group addition
Liquid, every group sets 3 multiple rooms.DMEM culture solutions 500 μ l, 37 DEG C, 5%CO containing 15% calf serum is added in lower room2Culture is for 24 hours
Afterwards, the cell on filter membrane upper layer is erased with cotton swab, filter membrane fixes 5min with methanol.With Giemsa dyeings 15min.100 times
The cell number through the membrane in 5 different visuals field, averages, drug is calculated as follows to tumour in being selected up and down under light microscopic
The transfer ability of cell.Inhibition of metastasis rate=(1- experimental groups average mobility cell number/control group average mobility cell number) ×
100%.
Four, colony formation
For trying cell：CDH6 prepared by step 1 is overexpressed osteosarcoma cell line；And as a contrast to 143B cells
In be transferred to the unloaded control cells of pcDNA3-FLAG empty carriers.
The each group cell of logarithmic growth phase with 0.25% trypsin digestion and is blown and beaten into individual cells respectively, and handle
Cell is suspended in spare in the DMEM culture solutions of 10% fetal calf serum.By cell suspension make gradient multiple dilution, every group of cell with
It is inoculated in the ware of 37 DEG C of pre-temperature culture solutions containing 10mL per the Graded Density of 100 cells of ware, and gently rotates respectively, make cell
It is uniformly dispersed.Set 37 DEG C of 5%CO2And it is cultivated 2~3 weeks in the cell incubator of saturated humidity.Often observation, when going out in culture dish
When existing macroscopic clone, culture is terminated.Liquid is discarded supernatant, is carefully embathed with PBS 2 times.4% paraformaldehyde is added to fix cell
5mL fixes 15 minutes.Then fixer is removed, adds appropriate GIMSA applications dyeing liquor to contaminate 10~30 minutes, is then slowly washed with flowing water
Dyeing liquor is removed, is air-dried.Plate is inverted and is superimposed a transparent film with grid, with the naked eye directly counts clone, or
Clone's number more than 10 cells is counted in microscope (low power lens).Finally calculate cloning efficiency.Cloning efficiency=(clone
Number/inoculating cell number) × 100%.
Five, result
1, CDH6 promotes the invasion of osteosarcoma cell
Can the present invention assesses CDH6 by Matrigel Matrigels adjust the phenotype of osteosarcoma cell line.Tables of data
Bright, CDH6, which is overexpressed expression, can promote the invasion characteristic (Fig. 1) of osteosarcoma cell line.
2, CDH6 promotes the migration of osteosarcoma cell
The present invention can influence to study for CDH6 using scratch experiment on the migration of osteosarcoma cell line.Study table
Bright, CDH6 is overexpressed the migration (Fig. 2) that can remarkably promote osteosarcoma cell line.
3, CDH6 can promote the proliferation of osteosarcoma cell
The present invention uses colony formation, and the ability that osteosarcoma cell is adjusted to CDH6 is studied.Experimental data table
Bright, CDH6 can remarkably promote the clonality (Fig. 3) of osteosarcoma cell line.This is consistent with above-mentioned experimental result,
Display CDH6 plays a significant role in osteosarcoma progression.
Embodiment 2, CDH6 and Patients with Osteosarcoma clinical prognosis are closely related
One, patient and sample
Present study be by Chinese People's Liberation Army General Hospital institutional review board approval (Beijing, China) and and
It is carried out under patient's informed consent.133 osteosarcoma and cancer beside organism on the basis of pathology and iconography standard are studied into
Evaluation is gone.Clinical information is recorded from patient assessment.Total life span is defined as from operation to the dead time.Patient
Follow-up Data monthly update.Sample is divided into two parts：A part is freezed immediately in liquid nitrogen, is stored in -80 DEG C until carrying out
RNA is extracted, and another part is then used for histopathological evaluation.Table 1 lists the clinic and demography of CDH6 in research population
Feature.
1 CDH6 of table expression and Patients with Osteosarcoma clinical information
Note：P-values uses Pearson Chi-square Tests.*P<0.05,**P<0.01.
Two, histopathological evaluation
Haematoxylin eosin stains (H＆E)：Tissue is fixed on 4% paraformaldehyde and buffers (20% with EDTA decalcifications after 48 hours
EDTA, pH 7.4).Tissue carries out paraffin embedding, slice, H＆E dyeing.Specific steps：Flowing water rinses after haematoxylin dyeing 5min
Flowing water rinses 10-30s, distilled water flushing 1-2s after 1-3s, 1% acidic alcohol 1-3s, and 0.5% Yihong liquid carries out dyeing 1-3min
Afterwards, it is placed in distilled water and is rinsed 1-2s, mounting, microscopically observation detection are carried out after dehydration.
Three, immunohistochemical staining
The slice fixed before is carried out baking 10min on (1) 72 DEG C of roasting piece machine.
(2) baked slice is cooled to room temperature, gradually in dimethylbenzene I, dimethylbenzene II, ethyl alcohol 100%, alcohol 95 %, second
Alcohol 85%, ethyl alcohol 75%, distilled water, 3% H2O2Middle processing 5min, dewaxes.
(3) sample, which is soaked in, repairs in liquid, to rigid boiling in micro-wave oven, suspends 5min, then opens micro-wave oven to rigid boiling, then stops
5min adds up 3-4 times, and overall length 30min is cooled to room temperature.
Source catalase in (4) 3% places to go hydrogen peroxide treatment number min.37 DEG C are closed 30min, spare.
(5) it closes：Goat-anti closes working solution, 37 DEG C of closing 30min.
(6) antibody response：CDH6 antibody (1:50 dilutions) 37 DEG C be incubated 2-3h, secondary antibody and three it is anti- reacts 10min,
(7) DAB develops the color：It will develop the color in liquid (A, B, C) each one after another drop of PBS to 1mL, mixing is evenly coated in tissue.Room
Temperature places 10-15min.
(8) core is contaminated：Hematoxylin contaminates core 1-2min, and then washing is anti-blue.
(9) break up：Histotomy after dye core is washed into 3min, 3 times, is put in differentiation liquid differentiation about 1min.So washing is whole
Only break up.
(10) mounting, microscopy：The slice broken up with neutral gum carries out mounting, microscopy after being dehydrated.
Graded using the German sxemiquantitative points-scoring system accepted extensively at present, and to staining power and areal extent into
Row is considered：0, dye-free；1, weak dyeing；2, moderate dyeing；3, it is strong to dye；It is respectively 0 (＜ 5%), 1 (5%- to dye percentage
25%), 2 (25%-50%), 3 (51%-75%) and 4 (>75%).The two fractional multiplications are last appraisal result.For more
Good is detected, we define 0 point as feminine gender, and 1-12 is the positive.
Four, qRT-PCR
(1) Total RNAs extraction：Tissue is cleaned once with 1 × PBS.1ml Trizol are added again, are uniformly mixed, in room temperature
Lower cracking 5min.0.2ml chloroforms are added according to every ml Trizol liquid, then acutely oscillation 50 times, stand 2-3min,
12000rpm centrifuges 15min.It takes in the as clear as crystal liquid in upper layer to new EP pipes, and adds isometric isopropanol, place -80 DEG C
Middle 15min is placed in 4 DEG C of centrifuge high speed centrifugation 15min；RNA white depositions, 4 DEG C of high speed centrifugations are washed with 75% ethyl alcohol
5min；And add absolute ethyl alcohol 1ml, 4 DEG C of high speed centrifugation 2min；It is spontaneously dried to RNA；Finally, RNA precipitate is dissolved, using 100
μ l DEPC water dissolutions.
(2) reverse transcription：2 μ g of total serum IgE, are added the random primer of 50 μM of 1 μ l, and 72 DEG C of progress unwindings are naturally cold after 5min
But room temperature is arrived.Then dNTP, reverse transcriptase M-MLV, RNase inhibitor RT Buffer is added, adds water to final system body
Product, is placed in 42 DEG C of constant temperature, reacts 1h, 95 DEG C of isoperibols, and 5min inactivation treatments finally obtain the cDNA of reverse transcription completion.
(3)RT-qPCR：PCR reaction solution (20 μ l systems) is prepared by following component：10μl SYBR Green Mix(2
×), 2 μ l cDNA, 0.4 μ l upstream and downstream primers (10 μM), the corresponding polishing of remainder deionized water；Sample is added to Real-
After in the special PCR pipes of time PCR, the PCR reaction conditions of setting ABI Prism SDS 7000 are：95 DEG C of 5min, 95 DEG C of 30s,
60℃30s,40cycles.Solution curve is melted after completion Real-time PCR to it analyze and combine Agarose gel analysis PCR
Whether product is special.By 2-ΔΔCtFormula gene expression values carry out data and calculate analysis.β-actin are used as internal reference.
Primer for detecting CDH6：
CDH6-F：5’-AAGGAGGTTTACACAGCCACTGT-3’；
CDH6-R：5’-CTTGGTACTGCTCCCTGTTTTCT-3’.
Primer for detecting internal reference β-actin：
β-actin-F：5’-ATCACCATTGGCAATGAGCG-3’；
β-actin-R：5’-TTGAAGGTAGTTTCGTGGAT-3’.
Six, result
To probe into specific effects of the CDH6 in osteosarcoma, we have evaluated 133 patients using histopathology
The expression (A in Fig. 4) of CDH6 in osteosarcoma tissue and cancer beside organism.Immunohistochemistry appraisal result is shown, with canceration group
It knits and compares, CDH6 expresses significantly up-regulation (p=3.6 × 10 in osteosarcoma tissue-6) (B in Fig. 4).QRT-PCR also turns out CDH6
Significantly up-regulation (C in Fig. 4) is expressed in osteosarcoma tissue.We have further inquired into clinical meanings of the CDH6 in Patients with Osteosarcoma
Justice, and have studied the relationship between the level of CDH6 and clinical pathologic characteristic.Statistics indicate that CDH6 expression and tumor tissues credit
Grade is closely related (table 2) with size.In addition, Kaplan Meier survival analysis shows CDH6 expressions in Patients with Osteosarcoma
Low patient has preferable DFS phase (p=0.024) and overall survival (p=relative to the patient of high expression CDH6
0.018) (D and E in Fig. 4).To sum up, these are the result shows that CDH6 plays a significant role in the prognosis and transfer of osteosarcoma.
<110>Chinese People's Liberation Army General Hospital
<120>CDH6 promotes Growth of Osteosarcoma and transfer
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Claims (9)
- Application of any one of the substance shown in following 1. (1)-(3) in following (a)-(e) is at least one：(1) CDH6 albumen；(2) nucleic acid molecules of CDH6 albumen are encoded；(3) contain expression cassette, recombinant vector or the transgenic cell of the nucleic acid molecules；(a) promote osteosarcoma cell invasion, or prepare the product for promoting osteosarcoma cell to invade；(b) promote osteosarcoma cell migration, or prepare the product for promoting osteosarcoma cell to migrate；(c) promote human osteosarcoma cell proliferation, or prepare the product for promoting human osteosarcoma cell proliferation；(d) promote Growth of Osteosarcoma, or prepare the product for promoting Growth of Osteosarcoma；(e) promote bone and flesh tumor metastasis, or prepare the product for promoting bone and flesh tumor metastasis.
- 2. the substance that following (1) or (2) expression and/or activity improve answering in following (a)-(e) is at least one can be promoted With：(1) CDH6 albumen；(2) nucleic acid molecules of CDH6 albumen are encoded；(a) promote osteosarcoma cell invasion, or prepare the product for promoting osteosarcoma cell to invade；(b) promote osteosarcoma cell migration, or prepare the product for promoting osteosarcoma cell to migrate；(c) promote human osteosarcoma cell proliferation, or prepare the product for promoting human osteosarcoma cell proliferation；(d) promote Growth of Osteosarcoma, or prepare the product for promoting Growth of Osteosarcoma；(e) promote bone and flesh tumor metastasis, or prepare the product for promoting bone and flesh tumor metastasis.
- 3. application according to claim 1 or 2, it is characterised in that：The product for promoting osteosarcoma cell to invade For invasive ability enhancing osteosarcoma cell model, or be used to prepare invasive ability enhancing osteosarcoma cell model object Matter；And/orThe product for promoting osteosarcoma cell to migrate is the osteosarcoma cell model of transfer ability enhancing, or is used for Prepare the substance of the osteosarcoma cell model of transfer ability enhancing；And/orThe product for promoting human osteosarcoma cell proliferation is the osteosarcoma cell model of proliferative capacity enhancing, or is used for Prepare the substance of the osteosarcoma cell model of proliferative capacity enhancing；And/orThe product for promoting Growth of Osteosarcoma is the animal model of Growth of Osteosarcoma ability enhancing, or is used to prepare The substance of the animal model of Growth of Osteosarcoma ability enhancing；And/orThe product for promoting bone and flesh tumor metastasis is the animal model of osteosarcoma transfer ability enhancing, or is used to prepare The substance of the animal model of osteosarcoma transfer ability enhancing.
- 4. can inhibit the substance that following (1) or (2) expression and/or activity reduce in following (a ')-(e ') is at least one Using：(1) CDH6 albumen；(2) nucleic acid molecules of CDH6 albumen are encoded；(a ') inhibits osteosarcoma cell invasion, or prepares the product for inhibiting osteosarcoma cell to invade；(b ') inhibits osteosarcoma cell migration, or prepares the product for inhibiting osteosarcoma cell to migrate；(c ') inhibits human osteosarcoma cell proliferation, or prepares the product for inhibiting human osteosarcoma cell proliferation；(d ') inhibits Growth of Osteosarcoma, or prepares the product for inhibiting Growth of Osteosarcoma；(e ') inhibits bone and flesh tumor metastasis, or prepares the product for inhibiting bone and flesh tumor metastasis.
- 5. application according to claim 4, it is characterised in that：The product is drug or health products.
- 6. any one of substance is as treating and/or preventing answering in the target of osteosarcoma shown in following (1)-(2) With：(1) CDH6 albumen；(2) nucleic acid molecules of CDH6 albumen are encoded.
- 7. according to any application in claim 1-6, it is characterised in that：CDH6 albumen behaviour source CDH6 albumen.
- 8. application according to claim 7, it is characterised in that：The CDH6 albumen is following any：(A1) amino acid sequence is the protein of SEQ ID No.1；(A2) substitution by amino acid sequence shown in SEQ ID No.1 by one or several amino acid residues and/or missing And/or addition and protein with the same function；(A3) with (A1)-(A2) in it is any defined by amino acid sequence have 99% or more, 95% or more, 90% or more, 85% or more or 80% or more homology and protein with the same function；(A4) fusion protein obtained after the N-terminal of protein defined by any in (A1)-(A3) and/or C-terminal connection label.
- 9. application according to claim 7, it is characterised in that：The nucleic acid molecules of the coding CDH6 albumen are following any The DNA molecular：(a1) DNA molecular shown in SEQ ID No.2；(a2) hybridize under strict conditions with (a1) DNA molecular limited and encode the DNA molecular of the CDH6 albumen；(a3) have 99% or more, 95% or more, 90% or more, 85% or more with the DNA sequence dna of any restriction in (a1)-(a2) Or 80% or more homology and the coding CDH6 albumen DNA molecular.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101772511A (en) * | 2007-02-16 | 2010-07-07 | 太平洋艾瑞有限公司 | Blocking the migration or metastasis of cancer cells by affecting adhesion proteins and the uses of new compounds thereof |
| CN102144163A (en) * | 2008-04-10 | 2011-08-03 | 麻省理工学院 | Methods for identification and use of agents targeting cancer stem cells |
| CN104220595A (en) * | 2012-04-04 | 2014-12-17 | 株式会社英仙蛋白质科学 | Conjugate of anti-CDH3 (P-cadherin) antibody and drug |
| CN106573061A (en) * | 2014-04-30 | 2017-04-19 | 佩德罗巴里德拉玛泽康德德费诺萨基金会 | Agent, product and use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101772511A (en) * | 2007-02-16 | 2010-07-07 | 太平洋艾瑞有限公司 | Blocking the migration or metastasis of cancer cells by affecting adhesion proteins and the uses of new compounds thereof |
| CN102144163A (en) * | 2008-04-10 | 2011-08-03 | 麻省理工学院 | Methods for identification and use of agents targeting cancer stem cells |
| CN104220595A (en) * | 2012-04-04 | 2014-12-17 | 株式会社英仙蛋白质科学 | Conjugate of anti-CDH3 (P-cadherin) antibody and drug |
| CN106573061A (en) * | 2014-04-30 | 2017-04-19 | 佩德罗巴里德拉玛泽康德德费诺萨基金会 | Agent, product and use |
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| QUANBO JI ET AL.,: "miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6.", 《MOLECULAR THERAPY》 * |
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