Secreted Factors from CD36+ Fibroblasts Induce Tumor Suppression in Subtypes of Breast Cancer

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Jabbari, Kosar

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2021

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Dissertation

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Human breast cancers are not fully autonomous. They are dependent on nutrients and growth-promoting signals provided by stromal cells. In order to instruct the surrounding cells to provide essential growth factors, cancer cells co-opt normal signaling molecules and mechanisms. To inhibit or potentially reverse tumor growth, our goal is to emulate this signaling and reprogram the microenvironment. For example, in a healthy mammary gland, fibroblasts (FBs) overexpress CD36; the downregulation of CD36 is one of the hallmarks of cancer-associated FBs. Therefore, in this project, we hypothesized that signaling from CD36+ FBs could cause growth suppression in a subset of breast cancer cell lines. We then designed a series of experiments to validate this growth suppression and elucidate secreted factors by CD36+ FBs that induce growth suppression. These experiments suggested three protein ligands of SLIT3, FBLN1, and PENK induce growth suppression in a subset of breast cancer subtypes.

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