Regulation of inflammatory factors by double-stranded RNA receptors in breast cancer cells
| Autor: | Amritha K. Venkatesh, Fabian Benencia, Harika Nandigam, Maria Muccioli, Michelle Pate, Tiffany Loftus, Manindra Singh, Deana Lewis |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Immunology Breast Neoplasms Biology 03 medical and health sciences Mice 0302 clinical medicine Cancer stem cell Cell Movement Immunology and Allergy Animals Humans Antigen-presenting cell Inflammation Tumor microenvironment Mice Inbred BALB C CD40 Hematology DNA Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis Receptors Pattern Recognition Cancer cell Interleukin 12 Myeloid-derived Suppressor Cell biology.protein MCF-7 Cells Female Chemokines Inflammation Mediators Neoplasm Transplantation |
| Zdroj: | Immunobiology. 223(6-7) |
| ISSN: | 1878-3279 |
| Popis: | Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others. Contrariwise, tumor-associated myeloid cells (myeloid-derived suppressor cells [MDSCs], dendritic cells [DCs], macrophages) or lymphoid cells such as regulatory T cells can stimulate tumor growth via inhibition of immune responses against the tumor or by participating in tumor neoangiogenesis. Herewith we analyzed the chemokine profile of mouse breast tumors regarding their capacity to generate factors capable of attracting and sequestering DCs to their midst. Chemoattractants from tumors were investigated by molecular biology and immunological techniques and tumor infiltrating DCs were investigated for matched chemokine receptors. In addition, we investigated the inflammatory response of breast cancer cells, a major component of the tumor microenvironment, to double-stranded RNA stimulation. By using molecular biology techniques such as qualitative and quantitative PCR, PCR arrays, and immunological techniques (ELISA, cytokine immunoarrays) we examined the effects of dsRNA treatment on the cytokine secretion profiles of mouse and human breast cancer cells and non-transformed cells. We were able to determine that tumors generate chemokines that are able to interact with receptors present on the surface of tumor infiltrating DCs. We observed that PRR signaling is able to modify the production of chemokines by breast tumor cells and normal breast cells, thereby constituting a possible player in shaping the profile of the leukocyte population in the TME. |
| Databáze: | OpenAIRE |
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