Method for restraining infiltration and metastasis of breast cancer cells by using target CCL 18 and application thereof

A breast cancer cell-targeted technology, applied in pharmaceutical formulations, gene therapy, antibodies, etc., can solve the problems of not being able to completely prevent breast cancer recurrence and metastasis, preventing breast cancer infiltration and metastasis, and not being able to clear TAM, so as to achieve the goal of treating breast cancer Cancer, improved prognosis, extended range of effects

Active Publication Date: 2010-06-23
崧铂(广州)生物医药有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Since TAM exists in a large amount in the microenvironment of metastatic or recurrent breast cancer tissue, many treatments cannot clear TAM and prevent the invasion and metastasis of breast cancer.
TAM is not sensitive to radiotherapy, and radiotherapy has a limited range of action as a local treatment; chemotherapy is effective for rapidly proliferating breast cancer cells, but not for TAM in the terminal stage of differentiation; endocrine therapy is only effective for estrogen receptor-positive cells but not For the treatment of estrogen receptor-negative breast cancer, it is ineffective for TAM; although surgical treatment is the gold standard for breast cancer treatment, it can significantly reduce the tumor burden, but for TAM in micrometastases, surgery is out of reach , cannot completely prevent the recurrence and metastasis of breast cancer, and finally make TAM the source of tumor metastasis and recurrence

Method used

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  • Method for restraining infiltration and metastasis of breast cancer cells by using target CCL 18 and application thereof
  • Method for restraining infiltration and metastasis of breast cancer cells by using target CCL 18 and application thereof
  • Method for restraining infiltration and metastasis of breast cancer cells by using target CCL 18 and application thereof

Examples

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Effect test

Embodiment 1

[0051] Example 1: The number of TAMs expressing CCL18 in the microenvironment of breast cancer tissue is related to the invasion and metastasis of breast cancer, and is negatively correlated with the prognosis of patients

[0052] In order to study the relationship between the expression of CCL18 by TAM and the prognosis of breast cancer patients, 562 cases of breast cancer patients' surgical resection specimens were collected and a series of related experiments were done. The experimental results are shown in figure 1 , figure 1 It is an experimental data graph showing that the number of TAMs expressing CCL18 in the microenvironment of breast cancer tissue is related to the invasion and metastasis of breast cancer, and is negatively correlated with the prognosis of patients.

[0053] First, the number of TAMs expressing CCL18 in the microenvironment of breast cancer was analyzed by immunohistochemistry, and the results are shown in figure 1 A and figure 1 B, figure 1 A is ...

Embodiment 2

[0056] Example 2: In vivo experiments confirming that CCL8 promotes breast cancer cell invasion and metastasis

[0057] We inoculated breast cancer cells under the mammary fat pad of NO-SCID mice, injected them locally with CCL18 (0.5 μg / ml), non-related chemokine CCL20 (0.5 μg / ml), and PBS, and set up an untreated group , injected once every three days for about five weeks, then sacrificed the mice, took the lungs of the experimental mice, and weighed the wet weight of the lungs. The results showed that the wet weight of the lungs in the CCL18 group was significantly increased compared with other groups; The tumors and metastases were made into paraffin sections, stained with HE, and the infiltration and metastasis of breast cancer were observed under a light microscope. The results showed that the primary tumor in the CCL18 group broke through the basement membrane, and large-scale lung metastasis occurred, which further indicated that CCL18 promotes the infiltration and meta...

Embodiment 3

[0058] Example 3: Related experiments to study the effect of IL-4-activated macrophages on breast cancer cells

[0059] Current studies suggest that TAMs highly express CCL18, and the phenotype and function of TAMs are similar to those of IL-4-activated macrophages. We used different methods to confirm that IL-4-activated macrophages are similar to TAMs and highly express CCL18. We established a co-culture model of IL-4-activated macrophages and breast cancer cells in transwell culture plates to simulate the microenvironment of breast tumors, and studied the effect of IL-4-activated macrophages on breast cancer cells.

[0060] Isolate mononuclear cells from normal adult peripheral blood by density gradient centrifugation, remove non-adherent lymphocytes in the culture plate, add DMEM medium containing 10% fetal bovine serum, culture in a 37-degree incubator for 3 days, replace After the culture medium, add IL-4 (45ng / ml) to induce IL-4-activated macrophages (Aa), LPS (25ug / ml)...

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Abstract

The invention provides a method for restraining infiltration and metastasis of breast cancer cells by using a target promoting tumour progression factor CCL 18, which is characterized by restraining the action of the CCL18 from tumour related macrophage in a target mode, and specifically, a neutralization antibody of a CCL8 or the siRNA of silent CCL18 mRNA is utilized to restrain the action of the CCL 18. The invention also provides a medicament for restraining the infiltration and metastasis of breast cancer cells, which contains components restraining the action of the CCL 18, comprising the neutralization antibody of the target CCL 18 or the siRNA of the CCL18 mRNA. The invention ensures that the treatment of CCL 18 secreted by a target TAM has general application value and overcomes the selectivity of Drug therapy to cases of breast cancer. The invention provides the method taking the CCL 18 as a target spot, makes up the defects of operation, radiotherapy, chemotherapy and endocrine therapy, and enlarges the range of target therapy.

Description

technical field [0001] The invention relates to the field of tumor targeting therapy, in particular to a method for inhibiting breast cancer cell infiltration and metastasis by targeting the tumor-associated macrophage (TAM) secreted CCL18 and its application. Background technique [0002] Breast cancer metastasis is the main reason for the failure of tumor therapy, and now studies suggest that tumor-associated macrophages (TAM) in the tumor microenvironment promote breast cancer metastasis and are negatively correlated with patient prognosis. At present, the treatment of breast cancer mainly includes surgery, chemotherapy, radiotherapy, endocrine therapy and targeted therapy, but none of these methods can completely prevent the invasion and metastasis of breast cancer. Therefore, comprehensive treatment methods are currently used clinically, and the specific implementation plan adopted is as follows: For a breast cancer patient, neoadjuvant chemotherapy is firstly performed...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K48/00A61P15/14A61P35/00A61P35/04
Inventor 宋尔卫陈静琦
Owner 崧铂(广州)生物医药有限责任公司
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