Biochemical Changes in the Niche Following Tumor Cell Invasion

Abstract

Metastatic cancer is the leading cause of all cancer related deaths. Prostate cancer (PCa) metastasizes preferentially to the bone marrow, specifically within the endosteal niche. Endosteal cells secrete homing molecules that may recruit PCa cells to the bone marrow. Once there, the biochemical signature of this niche regulates PCa fate including cellular dormancy or cell cycle arrest, reactivation and resistance to chemotherapeutics. Growth factors, interleukins, adhesion molecules, as well as extra-cellular matrix proteins can collectively change the phenotype of PCa cells. Understanding the biochemical signature of endosteal niche parasitism by PCa is imperative for the establishment of new and innovative therapeutic strategies. This review seeks to summarize these important niche signatures and the potential therapeutic approaches to target metastatic PCa within the bone marrow hematopoietic stem cell (HSC) niche. J. Cell. Biochem. 118: 1956-1964, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: DISSEMINATED TUMOR CELL (DTC); METASTASIS; NICHE; OSTEOBLAST; PROSTATE CANCER (PCa).

Figure 1. Summary of the molecular interactions of PCa cells in the bone marrow microenvironment

IL-6 = Interleukin 6; VEGF = Vascular endothelial growth factor; CXCL12 = SDF-1 = Stromal derived factor 1; CXCR4= CXC chemokine receptor 4; TGF-β = Transforming growth factor β; RANK = Receptor activator of nuclear factor kappa-B; TAMR = TYRO3, AXL, MERTK receptor; GAS6 = Growth arrest specific 6; EGF = Epithelial growth factor; IGF = Insulin growth factor; ECM = Extracellular matrix.