肿瘤微环境与耐药的发生在恶性血液病中研究进展

Tumor microenvironment and drug resistance in hematologic malignancies

肿瘤微环境与肿瘤细胞相互作用可以导致肿瘤细胞发生耐药,称为肿瘤微环境介导的细胞耐药(EM-DR)。EM-DR主要包括细胞黏附介导的耐药(CAM-DR)、可溶性因子介导的耐药(SM-DR)和其它途径诱导的耐药。SM-DR涉及大量的因子,这些因子主要通过促进恶性血细胞存活与增殖,抑制恶性血细胞凋亡导致细胞对药物不敏感。CAM-DR的研究主要通过肿瘤耐药细胞模型完成的,常见模型包括:球形模型、FN模型、间质模型。通过对模型研究发现肿瘤微环境可通过不同信号通路向细胞提供存活信号,从而导致耐药发生。另外肿瘤微环境还可调节耐药基因表达或局部的pH值诱导恶性血细胞发生耐药。本文就肿瘤微环境介导的恶性血液病细胞耐药的研究进展做一综述。

Interaction between Tumor microenvironment and tumor cell may lead to drug resistance, which is called environment mediated-drug resistance （EM-DR）. EM-DR mainly includes cell adhension mediated drugresistance（CAM-DR） ,soluble factor mediated-drug resistance（SM-DR）and other mechanism mediated-drug resistance. SM-DR is related to many soluble factors which confers cell drug resistance by promoting cell survial and proliferation as well as inhibiting cell apoptosis. For studying CAM-DR, three EM-DR models including spheroid model, FN model and stromal model have been established. The studies of the three models showed that tumor microenvironment conferred cell drug resistance by utilizing divergent signaling pathways. In addition,tumor microenvironment can induce hematological malignancies cell drug-resistance by modulating the expression of drug-resistance gene,changing local pH and so on.