Stem cell and cancer stem cell games on the ECM field

Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role played by their niche that defines a domain-specific identity and functions. The major macromolecular components of any physiological niche are collectively referred to as Extra Cellular Matrix (ECM). Consequently, niche-determined governance of SC-CSC fate(s) is significantly wired by the ECM and its chemical undercurrents, which involve specific signaling cascades driving asymmetrical division and self-renewal, besides maintaining tissue and organ homeostasis. Cell transformation is often associated with variations in ECM composition and dynamics; although the distinction of whether these are a cause or an effect of the process is not clearly established. CSCs regulate altered ECM subtleties; these in turn support disease progression by providing the necessary cues to maintain CSC quiescence and regeneration yet drive cancer metastases. Further, the specific composition of altered ECM plays a critical role in metastatic dissemination and homing to specific secondary sites for tumor regeneration. The present review presents our understanding of modulation of SC and CSC interactions in their respective niche by ECM components, and a complementary focus of intonation of ECMbiochemistry by these cells in developing an aberrant phenotype. ABBREVIATIONS Stem cells (SCs); extra cellular matrix (ECM); cancer stem cells (CSCs); epithelial-to-mesenchymal transitions (EMT); basement membrane (BM); interstitial matrix (IM); fibroblast growth factor (FGF); epidermal growth factor (EGF); transforming growth factor-beta (TGFb); platelet-derived growth factor (PDGF), insulin-like growth factor (IGF); tumor necrosis factor a (TNFa); epidermal growth factor receptor(EGFR);matrixmetallo-proteinases(MMPs);basic fibroblast growth factor (bFGF); human embryonic stem cells (hESCs); lineage negative (Lin ); reactive oxygen species (ROS); cancer associated fibroblasts (CAFs); osteopontin (OPN), periostin (POSTN), secreted protein acidic and rich in cysteine (SPARC); thrombospondin-1 (TSP-1); hyaluronic acid (HA); sonic hedgehog (SHH); phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), mitogen activated kinase-like protein (MAPK); v-erb-b2 avian erthroblastic leukemia viral oncogene homolog 2 (ERBB2); hyaluronan-mediated motility receptor (HMMR). CONTENTS