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Application of CD146 and its antibody in diagnosis and treatment of triple negative breast cancer

A triple-negative breast cancer, antibody technology, applied in the application field of diagnosis and treatment of breast cancer, can solve the problems of tissue and organ damage, toxic side effects, lack of targeting, etc.

Inactive Publication Date: 2018-04-20
INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This type of drug has no targeting, and it will also cause damage to normal tissues and organs in the whole body, and has strong toxic and side effects.
In addition, although triple-negative breast cancer is more sensitive to chemotherapy drugs in the early stages of chemotherapy, the prognosis is still very poor

Method used

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  • Application of CD146 and its antibody in diagnosis and treatment of triple negative breast cancer
  • Application of CD146 and its antibody in diagnosis and treatment of triple negative breast cancer
  • Application of CD146 and its antibody in diagnosis and treatment of triple negative breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: CD146 is highly specifically expressed in tumor histopathological sections of patients with triple-negative breast cancer;

[0027] Cell adhesion molecules play an important role in the development of breast cancer. CD146 molecule is an important cell adhesion molecule related to angiogenesis and tumor metastasis. In order to study the role of CD146 in breast cancer, we performed immunohistochemical analysis on 90 breast cancer histopathological sections and found that CD146 molecules were highly expressed specifically in triple-negative breast cancer.

[0028] Main materials: Paraffin sections of tumor tissues from breast cancer patients, including 44 cases of triple-negative breast cancer and 46 cases of non-triple-negative breast cancer, all from Tianjin Cancer Hospital;

[0029]Main reagents: 4% paraformaldehyde, xylene, absolute ethanol, absolute methanol, hydrogen peroxide, PBS, mouse anti-CD146 monoclonal antibody AA4; the antibodies AA98, AA4, and AA...

Embodiment 2

[0043] Example 2: CD146 overexpression induces EMT in epithelial breast cancer cell MCF-7;

[0044] We chose the CD146-negative cell line MCF-7 cells (purchased from Shanghai Cell Bank, catalog number TCHu74) as the cell model, and found that the high expression of CD146 in malignant triple-negative breast cancer tissues is of great significance. MCF-7 is an epithelial breast cancer cell line with low malignancy, high degree of differentiation, and extremely weak cell migration ability. We overexpressed CD146 molecule in MCF-7, constructed and obtained two stable expression strains, B10 and A5, among which B10 expresses CD146 moderately, and A5 expresses CD146 highly. At the same time, we also transformed the empty vector into MCF-7 cells to construct a control stable strain Mock. The specific process is detailed as follows.

[0045] Main reagent: CD146cDNA (SEQ ID NO: 7) was originally a gift from Professor Judith P. Johnson of the University of Munich, France, and is curre...

Embodiment 3

[0053] Example 3: In an orthotopic breast cancer mouse model, CD146 overexpression promotes the formation of mammary gland tumors, reduces the degree of differentiation of tumors, and promotes in situ invasion and distant migration of tumors;

[0054] We used SCID / Beige to construct a mouse model of orthotopic transplantation of breast cancer, and found that the high expression of CD146 in vivo plays an important role in the occurrence and development of breast cancer.

[0055] Experimental method: 20 4-week-old female SCID / Beige mice (purchased from Victoria Lihua) were selected and randomly divided into 2 groups. Inject 1×10 into the mammary fat tissue pad 6 Mock or A5 cells derived from MCF-7 cells were resuspended in 50ulPBS and mixed with 50ul 2.5mg / ml Matrigel. Observed once a week, measure the length, width and height, in order to calculate the tumor volume. After 10 weeks, when the tumor-bearing mice became weak, all the mice were killed by neck dislocation, the tumo...

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Abstract

The invention relates to an application of CD146 and its antibody in diagnosis and treatment of triple negative breast cancer. The CD146 being a novel target of the triple negative breast cancer is proposed for the first time, and the anti-CD146 antibody may become a novel targeted drug for the treatment of like diseases, so the invention provides the application of the CD146 or the anti-CD146 antibody or functional forms of the antibody in the preparation of drugs for diagnosing and / or treating the triple negative breast cancer. The CD146 molecule is highly specifically expressed in triple negative breast cancer tissues, induces the transformation of epithelial cells of tumor cells into interstitial cells, and promotes the invasion and migration of tumors, so the action mechanism of the CD146 antibody in the treatment of the triple negative breast cancer is mainly to inhibit the interstitial cell characteristics of the triple negative breast cancer cells and reduce the metastasis andinvasion ability. Compared with conventional chemotherapeutic drugs, the anti-CD146 antibody has the advantages of small side effects, clear target and no systemic side effects.

Description

[0001] This application is a divisional application of the application number 201110412778.X and the invention name "CD146 and its antibody diagnosis and treatment of triple-negative breast cancer". technical field [0002] The invention belongs to the field of immunodiagnosis and biotherapy. Specifically, the present invention relates to the application of CD146 molecule and its antibody in the diagnosis and treatment of breast cancer. More specifically, the CD146 monoclonal antibody AA4 involved in the present invention can diagnose triple-negative breast cancer, and the function of the CD146 monoclonal antibody AA98 and its functional form is to inhibit the characteristics of interstitial cells and malignant characteristics of triple-negative breast cancer cells, thereby inhibiting tumor transfer invasion. Background technique [0003] Breast cancer is the most common and deadly malignancy in women. Nearly 1.3 million women worldwide suffer from breast cancer every year...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00A61P35/04
CPCC07K16/3092C07K2317/73
Inventor 阎锡蕴曾启群吴真真卢迪段红霞罗永挺杨东玲冯静
Owner INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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