title: The hypoxic microenvironment: A determinant of cancer stem cell evolution.
abstract: Tumors are often viewed as unique entities with specific behaviors. However, tumors are a mixture of differentially evolved subpopulations of cells in constant Darwinian evolution, selecting the fittest clone and allowing it to outgrow the rest. As in the natural environment, the niche defines the properties the fittest clones must possess. Therefore, there can be multiple fit clones because of the various microenvironments inside a single tumor. Hypoxia is considered to be a major feature of the tumor microenvironment and is a potential contributor to the cancer stem cell (CSC) phenotype and its enhanced tumorigenicity. The acidic microenvironment around hypoxic cells is accompanied by the activation of a subset of proteases that contribute to metastasis. Because of aberrant angiogenesis and the inaccessibility of their locations, hypoxic cells are less likely to accumulate therapeutic concentrations of chemotherapeutics that can lead to therapeutic resistance. Therefore, the targeting of the hypoxic CSC niche in combination with chemotherapy may provide a promising strategy for eradicating CSCs. In this review, we examine the cancer stem cell hypothesis and its relationship to the microenvironment, specifically to hypoxia and the subsequent metabolic switch and how they shape tumor behavior.
authors.affiliation: Oncohematology and Genetic Department, Molecular Biology of Cancer Group, Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain.
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.affiliation: Pathology Department, Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Lleonart
mesh_terms: D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D059016:Tumor Microenvironment
keywords: cancer stem cell; hypoxia; microenvironment; tumor evolution