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CD146 and antibody diagnosis thereof, and application in treating triple negative breast cancer

A technology for triple-negative breast cancer and breast cancer, which is applied in the field of diagnosis and treatment of breast cancer, and can solve problems such as lack of targeting, tissue and organ damage, and toxic and side effects

Inactive Publication Date: 2013-06-19
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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  • CD146 and antibody diagnosis thereof, and application in treating triple negative breast cancer
  • CD146 and antibody diagnosis thereof, and application in treating triple negative breast cancer
  • CD146 and antibody diagnosis thereof, and application in treating triple negative breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: CD146 is highly specifically expressed in tumor histopathological sections of patients with triple-negative breast cancer;

[0026] 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.

[0027] Main materials: paraffin sections of tumor tissues of 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;

[0028]Main reagents: 4% paraformaldehyde, xylene, absolute ethanol, absolute methanol, hydrogen peroxide, PBS, mouse anti-CD146 monoclonal antibody AA4; the antibodies AA98, AA4, and AA1 ...

Embodiment 2

[0042] Example 2: CD146 overexpression induces EMT in epithelial breast cancer cell MCF-7;

[0043] 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.

[0044] Main reagent: CD146 cDNA (SEQ ID NO: 7) was originally a gift from Professor Judith P. Johnson of the University of Munich, France, and can als...

Embodiment 3

[0052] 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;

[0053] 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.

[0054] 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 50ul PBS 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 tum...

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Abstract

The invention relates to CD146 and antibody diagnosis thereof, and an application thereof in treating triple negative breast cancers. For a first time, the invention provides that CD146 is a novel target of triple negative breast cancer, and an anti-CD146 antibody might become a novel targeting medicine for treating the disease. Therefore, the invention provides an application of CD146 or anti-CD146 antibody or a functional form of the antibody in preparing medicines used for diagnosing and / or treating triple negative breast cancers. CD146 molecules are subjected to specific high expression in triple negative breast cancer tissues, and induce the occurrences of transformation of epithelial cell to mesenchymal cell in tumor cells. Therefore, tumor invasion migration is promoted. Therefore, the mechanism for CD146 antibody to treat triple negative breast cancer is mainly that the CD146 antibody inhibits the mesenchymal cell characteristics of triple negative breast cancer, and reduces the metastasis invasion capacity thereof. Compared with common chemotherapy medicines, the anti-CD146 antibody has the advantages of low side effects and clear target. The anti-CD146 antibody does not cause whole-body side effect.

Description

technical field [0001] 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 [0002] Breast cancer is the most common and deadly malignancy in women. Nearly 1.3 million women worldwide suffer from breast cancer every year, and more than 400,000 women die of breast cancer metastasis and recurrence. The most aggressive subtype of breast cancer, called triple-negative breast cancer, is characterized by estrogen receptor ...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K48/00A61P35/00A61P35/04G01N33/574
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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