肿瘤微环境与结直肠癌干性调节相互作用的研究进展

Research Progress on Interaction between Tumor Microenvironment and Regulation of the Stemness of Colorectal Cancer

结直肠癌(CRC)是消化系统常见恶性肿瘤之一,肿瘤干细胞(CSCs)理论的提出为CRC的防治带来了新的希望。该理论认为:CSCs是CRC复发、转移的根源,只有消灭CSCs,才能真正消灭肿瘤细胞。但研究发现结直肠癌干细胞(CCSC)干性是受肿瘤微环境(TME)调控的一个动态过程。本文介绍了TME是如何参与CCSC干性调节的,简述了TME各细胞成分通过分泌各种调节蛋白分子参与肿瘤干性调节以及免疫耐受的形成,同时叙述了肠隐窝Wnt、Notch、BMP和Hedgehog信号通路如何相互协同、拮抗维持肠隐窝干细胞的增殖与分化。最后提出TME在CCSC干性状态的维持及肿瘤细胞去分化过程中起促进作用,CCSC干性的维持强烈依赖于来自其微环境的外部信号。只有同时针对CCSC及TME的靶向治疗,才能在消除CCSC的同时,阻止已分化肿瘤细胞去分化恢复其干性,而后者才是CRC靶向治疗的关键。

Colorectal cancer(CRC)is one of the most common malignant tumors in the digestive system.The theory of tumor stem cells(CSCs)brings new hope for the prevention and treatment of CRC.According to the theory,CSCs are the root of recurrence and metastasis of CRC.Only by eliminating CSCs can we really eliminate tumor cells.However,it was found that the dryness of colorectal cancer stem cells(CCSC)is a dynamic process regulated by tumor microenvironment(TME).This paper introduces how TME participates in the regulation of CCSC dryness,briefly describes that the components of TME participate in the regulation of tumor dryness and the formation of immune tolerance by secreting various regulatory protein molecules,and describes how the signal pathways of Wnt,Notch,BMP and Hedgehog in the intestinal crypt cooperate and antagonize each other to maintain the proliferation and differentiation of the intestinal crypt stem cells.Finally,we proposed that TME plays an important role in the maintenance of CCSC dryness and the dedifferentiation of tumor cells.The maintenance of CCSC dryness is strongly dependent on external signals from its microenvironment.Only targeted treatment for CCSC and TME can eliminate CCSC and prevent differentiated tumor cells from dedifferentiating to restore their dryness,which is the key to targeted treatment for CRC.