Cancer Stem Cells and the Tumor Microenvironment: Soloists or Choral Singers

A.      Albini; E.      Cesana; D.      M. Noonan

Abstract

The idea of cancer stem cell (CSC) has recently moved to the forefront of cancer research. There is still a lack of a widespread consensus on the of these cells, description and definition. The increasing literature on CSCs has compelled researchers worldwide to rewrite the natural history of cancer including those cells as principal players as well as to revise their views on tumor formation and progression. CSCs are tumor cell components that can initiate a new tumor after an apparent therapeutic eradication. A functional definition of cancer stem cell or cancer initiating cell is that of a cell which, when transplanted in a mouse model, can give rise to a tumor recapitulating the original one or even a phenotypically diverse tumor related to the tumor of origin. Since the characteristic asymmetric division of stem cells is somewhat anomalous in cancer, it might be advisable to refer to them as “stemloids”. Stemness in cancer is not as much as an identity but rather a status. There is increasing evidence of the importance of the tumor and the host microenvironment in conditioning the stem cell status itself. The cancer stem cell microenvironment may be the key in the development of therapeutic strategies. We must think in terms of targeting “standard” tumor cells, cancer stem cells, and also their niche and tumor microenvironment. Here we discuss some features of cancer stem cells, and the role of the microenvironment, envisaging a choral view of cancer stem cell development and-or latency, towards development of specific therapeutic approaches. Here we propose models of replication and quiescence and the modulation by cells, genes and miRNAs. We also summarize in a table surface markers useful for the identification and isolation of CSCs.

Keywords: Cancer stem cell, stemness control, microenvironment, surface markers, niche, matrigel, miRNA, models, Tumor, stemloids, phenotype, CD133, CD44, so-matic stem, tumorigenesis, tumor-initiating cells, progenitor cells, onco-suppressor gene, oncogene activation, histopathological characteristics, breast cancer, stem cells, che-motherapy, EHS sarcoma, retinoids, DMSO, bu-tyrrate, hypoxia, vascularization, Anti-angiogenic therapy, me-tastatic cascade, multipo-tent precursor down, acute myeloid leukemia, xenotransplan-tation, Leukemia Initiating Cells, carcinogenesis, apoptosis, epithelial ovarian cancers, Ewing sarcoma family tumors, arachidonate 5-lipoxygenase, 5-lipoxygenase inhibitor, Zileuton, polycomb repressor complex 2 (PRC2), 3-deazaneplanocin A, acute promyelocytic leu-kemia (APL), fibroblasts, telomerases, bone-hematopoietic interface, melanoma cells, Epithelial-to-Mesenchymal-Transition (EMT), immunohistochemical, mammary progenitor, cytokeratins, estrogen, cytotoxic agents, ATP-binding cassette, breast cancer-resistance protein (BCRP), non-Hodgkin's lymphomas, tyrosine, glioblastoma multiforme (GBM), glioblastoma stem cells, heparan sulfate proteoglycans