The Marrow Niche Controls the Cancer Stem Cell Phenotype of Disseminated Prostate Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 May 14

PMID 27172799

Citations 37

Authors

Yusuke Shiozawa

Janice E Berry

Matthew R Eber

Younghun Jung

Kenji Yumoto

Frank C Cackowski

Hyeun Joong Yoon

Princy Parsana

Rohit Mehra

Jingcheng Wang

Samantha McGee

Eunsohl Lee

Sunitha Nagrath

Kenneth J Pienta

Russell S Taichman

Affiliations

Soon will be listed here.

Abstract

Dissemination of cancer stem cells (CSCs) serves as the basis of metastasis. Recently, we demonstrated that circulating prostate cancer targets the hematopoietic stem cell (HSCs) 'niche' in marrow during dissemination. Once in the niche, disseminated tumor cells (DTCs) may remain dormant for extended periods. As the major function of the HSC niche is to maintain stem cell functions, we hypothesized that the niche regulates CSC activities of DTCs. Here we show that DTCs recovered from marrow were significantly enriched for a CSC phenotype. Critically, the conversion of DTCs to CSCs is regulated by niche-derived GAS6 through the Mer/mTOR; molecules previously shown to regulate dormancy. The data demonstrate that the niche plays a significant role in maintaining tumor-initiating prostate cancer in marrow and suggests a functional relationship between CSCs and dormancy. Understanding how the marrow niche regulates the conversion of DTCs to CSCs is critical for the development of therapeutics specifically targeting skeletal bone metastasis and dormancy.

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