1. Overexpression of CD36 in mammary fibroblasts suppresses colony growth in breast cancer cell lines.
- Author
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Cheng Q, Jabbari K, Winkelmaier G, Andersen C, Yaswen P, Khoshdeli M, and Parvin B
- Subjects
- Activins pharmacology, Cell Line, Tumor, Cell Polarity drug effects, Cell Proliferation drug effects, Cells, Cultured, Down-Regulation drug effects, Female, Fibroblasts drug effects, Fibroblasts pathology, Humans, Phosphorylation drug effects, Smad Proteins metabolism, Tumor Stem Cell Assay, YY1 Transcription Factor metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, CD36 Antigens metabolism, Fibroblasts metabolism, Mammary Glands, Human pathology
- Abstract
Human breast tumors are not fully autonomous. They are dependent on nutrients and growth-promoting signals provided by the supporting stromal cells. Within the tumor microenvironment, one of the secreted macromolecules by tumor cells is activin A, where we show to downregulate CD36 in fibroblasts. Downregulation of CD36 in fibroblasts also increases the secretion of activin A by fibroblasts. We hypothesize that overexpression of CD36 in fibroblasts inhibits the formation of solid tumors in subtypes of breast cancer models. For the first time, we show that co-culturing organoid models of breast cancer cell lines of MDA-MB-231 (e.g., a triple-negative line) or MCF7 (e.g., a luminal-A line) with CD36
+ fibroblasts inhibit the growth and normalizes basal and lateral polarities, respectively. In the long-term anchorage-independent growth assay, the rate of colony formation is also reduced for MDA-MB-231. These observations are consistent with the mechanism of tumor suppression involving the downregulation of pSMAD2/3 and YY1 expression levels. Our integrated analytical methods leverage and extend quantitative assays at cell- and colony-scales in both short- and long-term cultures using brightfield or immunofluorescent microscopy and robust image analysis. Conditioned media are profiled with the ELISA assay., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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