Carnero Amancio, Lleonart Matilde
Oncohematology and Genetic Department, Molecular Biology of Cancer Group, Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain.
Pathology Department, Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain.
Bioessays. 2016 Jul;38 Suppl 1:S65-74. doi: 10.1002/bies.201670911.
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.
肿瘤通常被视为具有特定行为的独特实体。然而，肿瘤是处于持续达尔文式进化中的不同进化亚群细胞的混合物，选择最适应的克隆并使其超越其他克隆生长。如同在自然环境中一样，生态位决定了最适应克隆必须具备的特性。因此，由于单个肿瘤内部存在各种微环境，可能会有多个适应克隆。缺氧被认为是肿瘤微环境的一个主要特征，并且是癌症干细胞（CSC）表型及其增强的致瘤性的潜在促成因素。缺氧细胞周围的酸性微环境伴随着有助于转移的一组蛋白酶的激活。由于异常血管生成以及其位置难以接近，缺氧细胞不太可能积累能够导致治疗抗性的化疗药物的治疗浓度。因此，将缺氧的癌症干细胞生态位与化疗相结合进行靶向治疗可能为根除癌症干细胞提供一种有前景的策略。在这篇综述中，我们研究了癌症干细胞假说及其与微环境的关系，特别是与缺氧以及随后的代谢转换的关系，以及它们如何塑造肿瘤行为。
