Interactions with Muscle Cells Boost Fusion, Stemness, and Drug Resistance of Prostate Cancer Cells.

Document Type

Article

Publication Date

3-1-2019

Institution/Department

Center for Molecular Medicine, Maine Medical Center Research Institute

Journal Title

Molecular cancer research : MCR

MeSH Headings

Cell Line, Tumor, Drug Resistance, Neoplasm, Humans, Male, Neoplastic Stem Cells, Prostatic Neoplasms

Abstract

Poorly understood interactions with nonmalignant cells within the tumor microenvironment play an important role in cancer progression. Here, we explored interactions between prostate cancer and muscle cells that surround the prostate. We found that coculturing of prostate cancer cells with skeletal or smooth muscle cells expands the subpopulations of cancer cells with features characteristic of cancer stem-like cells, including anchorage-independent growth, elevated CD133 expression, and drug resistance. These changes in the properties of cancer cells depend on: (i) the muscle cell-induced increases in the concentrations of interleukins 4 and 13; (ii) the cytokine-induced upregulation of the expression of syncytin 1 and annexin A5; and (iii) cancer cell fusion. In human prostate cancer tissues, expression of syncytin 1 and annexin A5, proteins that we found to be required for the cell fusion, positively correlated with the cancer development suggesting that these proteins can be used as biomarkers to evaluate cancer progression and potential therapeutic targets. IMPLICATIONS: The discovered effects of muscle cells on prostate cancer cells reveal a novel and specific pathway by which muscle cells in the microenvironment of prostate cancer cells promote cell fusion and cancer progression.

ISSN

1557-3125

First Page

806

Last Page

820

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