Title |
Effects of cytokines derived from cancer-associated fibroblasts on androgen synthetic enzymes in estrogen receptor-negative breast carcinoma
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Published in |
Breast Cancer Research and Treatment, August 2017
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DOI | 10.1007/s10549-017-4464-5 |
Pubmed ID | |
Authors |
Kyoko Kikuchi, Keely May McNamara, Yasuhiro Miki, Ju-Yeon Moon, Man Ho Choi, Fumiya Omata, Minako Sakurai, Yoshiaki Onodera, Yoshiaki Rai, Yasuyo Ohi, Yasuaki Sagara, Minoru Miyashita, Takanori Ishida, Noriaki Ohuchi, Hironobu Sasano |
Abstract |
The tumor microenvironment plays pivotal roles in promotion of many malignancies. Cancer-associated fibroblasts (CAFs) have been well-known to promote proliferation, angiogenesis, and metastasis but mechanistic understanding of tumor-stroma interactions is not yet complete. Recently, estrogen synthetic enzymes were reported to be upregulated by co-culture with stromal cells in ER positive breast carcinoma (BC) but effects of co-culture on androgen metabolism have not been extensively examined. Therefore, we evaluated roles of CAFs on androgen metabolism in ER-negative AR-positive BC through co-culture with CAFs. Concentrations of steroid hormone in supernatant of co-culture of MDA-MB-453 and primary CAFs were measured using GC-MS. Cytokines derived from CAFs were determined using Cytokine Array. Expressions of androgen synthetic enzymes were confirmed using RT-PCR and Western blotting. Correlations between CAFs and androgen synthetic enzymes were analyzed using triple-negative BC (TNBC) patient tissues by immunohistochemistry. CAFs were demonstrated to increase expressions and activities of 17βHSD2, 17βHSD5, and 5α-Reductase1. IL-6 and HGF that were selected as potential paracrine mediators using cytokine array induced 17βHSD2, 17βHSD5, and 5α-Reductase1 expression. Underlying mechanisms of IL-6 paracrine regulation of 17βHSD2 and 17βHSD5 could be partially dependent on phosphorylated STAT3, while phosphorylated ERK could be involved in HGF-mediated 5α-Reductase1 induction. α-SMA status was also demonstrated to be significantly correlated with 17βHSD2 and 17βHSD5 status in TNBC tissues, especially AR-positive cases. Results of our present study suggest that both IL-6 and HGF derived from CAFs could contribute to the intratumoral androgen metabolism in ER-negative BC patients. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 25 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 6 | 24% |
Researcher | 6 | 24% |
Student > Ph. D. Student | 4 | 16% |
Student > Master | 3 | 12% |
Professor | 1 | 4% |
Other | 2 | 8% |
Unknown | 3 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 9 | 36% |
Medicine and Dentistry | 4 | 16% |
Nursing and Health Professions | 3 | 12% |
Agricultural and Biological Sciences | 3 | 12% |
Chemical Engineering | 2 | 8% |
Other | 0 | 0% |
Unknown | 4 | 16% |