Regulation of prostate cancer progression by the tumor microenvironment.

Prostate cancer remains the most frequently diagnosed cancer in men in North America, and despite recent advances in treatment patients with metastatic disease continue to have poor five-year survival rates.

Recent studies in prostate cancer have revealed the critical role of the tumor microenvironment in the initiation and progression to advanced disease. Experimental data have uncovered a reciprocal relationship between the cells in the microenvironment and malignant tumor cells in which early changes in normal tissue microenvironment can promote tumorigenesis and in turn tumor cells can promote further pro-tumor changes in the microenvironment. In the tumor microenvironment, the presence of persistent immune infiltrates contributes to the recruitment and reprogramming of other non-immune stromal cells including cancer-associated fibroblasts and a unique recently identified population of metastasis-initiating cells (MICs). These MICs, which can also be found as part of the circulating tumor cell (CTC) population in PC patients, promote cancer cell transformation, enhance metastatic potential and confer therapeutic resistance. MICs act can on other cells within the tumor microenvironment in part by secreting exosomes that reprogram adjacent stromal cells to create a more favorable tumor microenvironment to support continued cancer growth and progression. We review here the current data on the intricate relationship between inflammation, reactive stroma, tumor cells and disease progression in prostate cancer.

Cancer letters. 2016 Jan 28 [Epub ahead of print]

Stephen L Shiao, Gina Chia-Yi Chu, Leland W K Chung

Departments of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.  Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

PubMed

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