Abstract
Recently, emerging evidence has suggested that carcinoma-associated fibroblasts (CAFs) could contribute to chemotherapy resistances in breast cancer treatment. The aim of this study is to compare the gene expression profiling of CAFs before and after chemotherapy and pick up candidate genes that might associate with chemotherapy resistance and could be used as predictors of treatment response. CAFs were cultured from surgically resected primary breast cancers and identified with immunohistochemistry (IHC) and Flow cytometry (FCM). MDA-MB-231 cells were cultured as the breast cancer cell line. Cell adhesion assay, invasion assay, and proliferation assay (MTT) were performed to compare the function of MDA-MB-231 cells co-cultured with CAFs and MDA-MB-231 cells without co-culture, after chemotherapy. Totally 6 pairs of CAFs were prepared for microarray analysis. Each pair of CAFs were obtained from the same patient and classified into two groups. One group was treated with Taxotere (regarded as after chemotherapy) while the other group was not processed with Taxotere (regarded as before chemotherapy). According to our study, the primary-cultured CAFs exhibited characteristic phenotype. After chemotherapy, MDA-MB-231 cells co-cultured with CAFs displayed increasing adhesion, invasiveness and proliferation abilities, compared with MDA-MB-231 cells without CAFs. Moreover, 35 differentially expressed genes (absolute fold change >2) were identified between CAFs after chemotherapy and before chemotherapy, including 17 up-regulated genes and 18 down-regulated genes. CXCL2, MMP1, IL8, RARRES1, FGF1, and CXCR7 were picked up as the candidate markers, of which the differential expression in CAFs before and after chemotherapy was confirmed. The results indicate the changes of gene expression in CAFs induced by Taxotere treatment and propose the candidate markers that possibly associate with chemotherapy resistance in breast cancer.
Highlights
Breast cancer is considered as the most common cancer in women, accounting for 29% of estimated new cancer cases and 14% of estimated cancer-related deaths [1]
Emerging evidences have suggested that carcinomaassociated fibroblasts (CAFs) could contribute to chemotherapy resistances in breast cancer treatment [3]
The notion is widely accepted that the development and progression of cancer highly depends on the interactions between tumor cells and tumor microenvironment
Summary
Breast cancer is considered as the most common cancer in women, accounting for 29% of estimated new cancer cases and 14% of estimated cancer-related deaths [1]. Chemotherapy is one of the cornerstone treatments in patients with breast cancer, which overall improves breast cancer outcome by 5–10% in patients with node negative disease [2]. Its use is increasingly affected by chemotherapy resistance and lack of effective predictors. Emerging evidences have suggested that carcinomaassociated fibroblasts (CAFs) could contribute to chemotherapy resistances in breast cancer treatment [3]. As the most frequent component of stroma cells in tumor microenvironment, CAFs have been assumed to play an important role in the carcinogenesis and development of breast cancer [4,5].
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