Application of IL1R2 in prognosis evaluation and targeted therapy of breast cancer

A breast cancer, use-of-use technology in oncology and diagnostics to address issues that limit the effectiveness of chemotherapy

Active Publication Date: 2019-03-15
FUDAN UNIV SHANGHAI CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in some patients, drug resistance problems that arise during chemotherapy greatly limit the efficacy of chemotherapy

Method used

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  • Application of IL1R2 in prognosis evaluation and targeted therapy of breast cancer
  • Application of IL1R2 in prognosis evaluation and targeted therapy of breast cancer
  • Application of IL1R2 in prognosis evaluation and targeted therapy of breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0183] Example 1: IL1R2 gene expression is significantly increased in breast cancer tissue

[0184] Firstly, the gene expression of ALDH+CD24-CD44+ breast cancer tumor stem cells obtained from human breast cancer xenograft tumor model mouse tumor tissue was detected by RNAseq. - Increased expression in CD44+ breast cancer tumor stem cell population.

[0185] In the human breast cancer cell line, ALDH+CD24-CD44+ breast cancer tumor stem cells were re-sorted, and the expression of IL1R2 mRNA and protein was increased in the breast cancer tumor stem cell population again ( figure 1 A and 1B).

[0186] Therefore, the expression of IL1R2 in the tumor tissues of 38 breast cancer patients was detected by immunohistochemistry, and it was found that the expression of IL1R2 in breast cancer cells in 32 of them (about 81.58%) was significantly higher than that in the corresponding normal breast epithelial cells ( figure 1 C).

[0187] Breast cancer tissue microarrays were used to dete...

Embodiment 2

[0198] Example 2: IL1R2 recruits tumor-associated macrophages through various cytokines

[0199] Studies have shown that tumor-associated macrophages (TAMs) can promote tumor growth, drug resistance and metastasis. The results of Example 1 show that the expression of IL1R2 in serum is related to the number of monocytes, and TAMs are derived from the differentiation of peripheral monocytes. Therefore, in this example, the enrichment of TAMs in transplanted tumor tissues was analyzed.

[0200] The expression of TAMs markers CD11b and MHC-II molecules in transplanted tumor tissues was analyzed by flow cytometry, and the results showed that the knockdown of IL1R2 significantly decreased the proportion of CD11b+MHC-II+TAMs in transplanted tumor cells ( image 3 A), while the overexpression of IL1R2 promoted the increase of TAMs in xenograft tumor tissues ( image 3 B). The results of the non-contact co-culture system showed that the culture supernatant of IL1R2 overexpressing cel...

Embodiment 3

[0207] Example 3: IL1R2 neutralizing antibody treatment can inhibit the malignant phenotype of human breast cancer cells

[0208] Knockdown of IL1R2 gene expression or overexpression of IL1R2 gene expression in human breast cancer cells by shRNA, the results show that IL1R2 can regulate the proliferation, invasion and self-renewal ability of tumor stem cells in breast cancer cells, and regulate breast cancer in immunodeficient mice Growth, metastasis, and infiltration of tumor-associated macrophages in xenografts. The role of IL1R2 is related to the regulation of BMI1 protein ubiquitination modification level and protein stability through deubiquitinating enzyme USP15. Therefore, the present inventors explored ways to target and inhibit the expression of IL1R2 in breast cancer.

[0209]The results showed that treating human breast cancer cell line SUM149 cells with an IL1R2 protein neutralizing antibody (R&D Company, product number: AF263) for 48 hours could significantly inh...

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Abstract

The invention relates to the application of IL1R2 in prognosis evaluation and targeted therapy of breast cancer. Specifically, the invention provides the application of an IL1R2 gene, mRNA, cDNA, a protein or a detection reagent thereof, wherein the IL1R2 gene, the mRNA, the cDNA, the protein or the detection reagent thereof are used for (i) detecting breast cancer or risk of breast cancer and / ora marker for breast cancer metastasis or risk of breast cancer metastasis, and / or (ii) preparing a diagnostic reagent or a kit for detecting breast cancer or the risk of breast cancer and / or breast cancer metastasis or the risk of breast cancer metastasis. A study shows that the IL1R2 can serve as a therapeutic target of breast cancer. The invention also provides the application of an inhibitor containing IL1R2, and the inhibitor is characterized by being used for preparing (i) a pharmaceutical composition for treating breast cancer and / or (ii) a pharmaceutical composition for preventing breast cancer metastasis.

Description

technical field [0001] The present invention relates to the field of oncology and diagnosis, in particular, the present invention relates to the application of IL1R2 in breast cancer treatment and prognosis assessment. Background technique [0002] Breast cancer is a common malignant cancer in women, which seriously endangers women's physical and mental health. Globally, more than 1.2 million women are estimated to be diagnosed with breast cancer each year. Although my country is a country with a low incidence of breast cancer, due to the huge population base, the absolute number of breast cancer patients is large; at the same time, my country has become one of the countries with the fastest growth in the incidence of breast cancer, making it an important place for women's health. A big killer. [0003] The mammary gland is not an important organ to maintain human life activities, and breast cancer in situ is not fatal; but because breast cancer cells lose the characteristi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574A61K45/00A61K31/337A61P35/00
CPCA61K45/00A61P35/00G01N33/57415A61K31/337C12Q1/6886C12Q2600/118C12Q2600/158G01N2800/52A61K2300/00
Inventor 柳素玲张立行强健坤
Owner FUDAN UNIV SHANGHAI CANCER CENT
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