title: Dynamic Interactions Between Cancer Stem Cells And Their Stromal Partners.
abstract: The cancer stem cell (CSC) paradigm presumes the existence of self-renewing cancer cells capable of regenerating all tumor compartments and exhibiting stem cell-associated phenotypes. Recent interpretations of the CSC hypothesis envision stemness as a dynamic trait of tumor-initiating cells rather than a defined and unique cell type. Bidirectional crosstalk between the tumor microenvironment and the cancer bulk is well described in the literature and the tumor-associated stroma, vasculature and immune infiltrate have all been implicated as direct contributors to tumor development. These non-neoplastic cell types have also been shown to organize specific niches within the tumor bulk where they can control the intra-tumor CSC content and alter the fate of CSCs and tumor progenitors during tumorigenesis to acquire phenotypic features for invasion, metastasis and dormancy. Despite the complexity of the tumor-stroma interactome, novel therapeutic approaches envision combining tumor-ablative treatment with manipulation of the tumor microenvironment. We will review the currently available literature that provides clues about the complex cellular network that regulate the CSC phenotype and its niches during tumor progression.
authors.affiliation: Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America ; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America.
authors.forename: Tea Soon
authors.initials: TS
authors.lastname: Park
authors.affiliation: University of Pittsburgh School of Medicine, Department of Cardiothoracic Surgery, Pittsburgh, Pennsylvania, United States of America ; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America ; McGowan Institute of Regenerative Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Vera S
authors.initials: VS
authors.lastname: Donnenberg
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America ; McGowan Institute of Regenerative Medicine, Pittsburgh, Pennsylvania, United States of America ; University of Pittsburgh School of Medicine, Department of Medicine, Division of Hematology/Oncology, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Donnenberg
authors.affiliation: Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America ; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America.
authors.forename: Elias T
authors.initials: ET
authors.lastname: Zambidis
authors.affiliation: Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America ; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Zimmerlin
keywords: Cancer stem cells; mesenchymal stem/stromal cells; tumor microenvironment; tumor progression; tumor-initiating cells