Atay Safinur, Godwin Andrew K
Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City, KS USA.
Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City, KS USA ; University of Kansas Cancer Center; Kansas City, KS USA.
Commun Integr Biol. 2014 Jan 1;7(1):e28231. doi: 10.4161/cib.28231. Epub 2014 Feb 27.
Intercellular communication is a key process in the development and progression of cancer. The dynamic and reciprocal interplays between the tumor and its microenvironment orchestrate events critical to the establishment of primary and metastatic niches and maintenance of a permissive environment at the tumor-stroma interface. Atay and colleagues found that gastrointestinal stromal tumor cells secrete vesicles known as exosomes. These exosomes contain oncogenic KIT and their transfer and uptake by surrounding smooth muscle cells lead to enhanced AKT and MAPK signaling and phenotypic modulation of several cellular processes, including morphological changes, expression of tumor-associated markers, secretion of matrix metalloproteinases, and enhanced tumor cell invasion. This provocative study emphasizes that exosome-mediated signaling within the tumor microenvironment acts as a positive feedback loop that contributes to invasiveness and that interfering with this message delivery system may represent promising therapeutic approaches, not only for GIST, but for other types of cancer.
细胞间通讯是癌症发生和发展的关键过程。肿瘤与其微环境之间动态且相互的作用，协调着对原发性和转移性微环境的建立以及在肿瘤-基质界面维持适宜环境至关重要的事件。阿泰及其同事发现，胃肠道间质瘤细胞分泌名为外泌体的囊泡。这些外泌体含有致癌性KIT，它们被周围平滑肌细胞转移和摄取后，会导致AKT和MAPK信号增强以及多个细胞过程的表型调节，包括形态变化、肿瘤相关标志物的表达、基质金属蛋白酶的分泌以及肿瘤细胞侵袭增强。这项引人深思的研究强调，肿瘤微环境中由外泌体介导的信号传导充当了促进侵袭性的正反馈回路，干扰这种信息传递系统可能代表着有前景的治疗方法，不仅适用于胃肠道间质瘤，也适用于其他类型的癌症。
