Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity.
Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity.
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DOI：
10.3109/03008207.2015.1066780
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发表时间：
2015
影响因子：
2.9
通讯作者：
Dallaglio K
中科院分区：
文献类型：
--
作者：
Albini A;Bruno A;Gallo C;Pajardi G;Noonan DM;Dallaglio K
能够重现肿瘤异质性的肿瘤细胞已经在不同的肿瘤类型中被追踪、分离和表征，并且通常被称为癌症干细胞或癌症起始细胞（CSC/CIC）。CSC/CIC在肿瘤块中扩散，并且对抗癌疗法和不利条件具有抗性。它们能够分裂成另一种干细胞和“增殖”癌细胞。它们似乎是疾病复发和转移性传播的原因，即使在原发性肿瘤明显根除后。肿瘤微环境（TUMIC）对CSC/CIC活性的调节仍然知之甚少。CSC/CIC可以以特殊和独特的方式与TUMIC相互作用，这取决于遇到的TUMIC细胞或蛋白质。TUMIC由细胞外基质成分以及细胞参与者组成，其中包括内皮细胞、基质细胞和免疫细胞，提供并响应来自CSC/CIC的信号。这种相互作用可能有助于CSC/CIC可能在组织中以休眠状态存在多年的机制，随后引起患者的肿瘤复发或转移。不同的TUMIC成分，包括结缔组织，可以在肿瘤的不同区域差异性地激活CIC/CSC，并有助于产生癌症异质性。在这里，我们回顾了肿瘤微环境的不同组成部分和CSC/CIC之间可能的网络活动，重点是它在肿瘤异质性和进展中的作用。我们还总结了新的治疗选择，可以靶向CSC/CIC和微环境，以逃避由CSC/CIC激活的耐药机制，负责疾病复发和转移。
Tumor cells able to recapitulate tumor heterogeneity have been tracked, isolated and characterized in different tumor types, and are commonly named Cancer Stem Cells or Cancer Initiating Cells (CSC/CIC). CSC/CIC are disseminated in the tumor mass and are resistant to anti-cancer therapies and adverse conditions. They are able to divide into another stem cell and a “proliferating” cancer cell. They appear to be responsible for disease recurrence and metastatic dissemination even after apparent eradication of the primary tumor. The modulation of CSC/CIC activities by the tumor microenvironment (TUMIC) is still poorly known. CSC/CIC may mutually interact with the TUMIC in a special and unique manner depending on the TUMIC cells or proteins encountered. The TUMIC consists of extracellular matrix components as well as cellular players among which endothelial, stromal and immune cells, providing and responding to signals to/from the CSC/CIC. This interplay can contribute to the mechanisms through which CSC/CIC may reside in a dormant state in a tissue for years, later giving rise to tumor recurrence or metastasis in patients. Different TUMIC components, including the connective tissue, can differentially activate CIC/CSC in different areas of a tumor and contribute to the generation of cancer heterogeneity. Here, we review possible networking activities between the different components of the tumor microenvironment and CSC/CIC, with a focus on its role in tumor heterogeneity and progression. We also summarize novel therapeutic options that could target both CSC/CIC and the microenvironment to elude resistance mechanisms activated by CSC/CIC, responsible for disease recurrence and metastases.