Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells
Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells
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DOI：
10.1158/0008-5472.can-05-3204
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Fais, S
中科院分区：
文献类型：
--
作者：
Lugini, L;Matarrese, P;Fais, S
细胞自食现象，通常是指其他细胞内的细胞吞噬，在恶性肿瘤中有描述，但其生物学意义在很大程度上仍然未知。在本研究中，我们调查了人黑色素瘤中同类相食的发生、体内相关性和潜在机制。作为第一个证据，我们观察到，在黑色素瘤的转移性病变中，肿瘤自食在体内可清楚地检测到，并且通常涉及T细胞，其可以在肿瘤细胞内的降解状态中发现。然后，体外实验证实，T细胞的同类相食是转移性黑色素瘤细胞的特性，但不是。原发性黑色素瘤细胞。特别是，形态学分析，包括延时摄影和电子显微镜，揭示了一系列事件，其中转移性黑色素瘤细胞能够吞噬和消化活的自体黑色素瘤特异性CD8（+）T细胞。重要的是，这种同类相食活动显著增加了转移性黑素瘤细胞的存活，特别是在饥饿条件下，这支持了肿瘤细胞可以使用活淋巴细胞的进食作为在低营养供应条件下“进食”的方式的证据。同类相食的机制涉及一个复杂的框架，包括溶酶体蛋白酶组织蛋白酶13的活性，小窝的形成，埃兹蛋白细胞骨架的完整性和功能。总之，我们的研究表明，人类转移性黑色素瘤细胞可以杀死活的T细胞，而不是编程杀死它们，这表明肿瘤免疫逃逸的新机制。此外，我们的数据表明，同类相食可能是一种“进食”活动，旨在维持恶性肿瘤细胞在不利的微环境中的生存和发展。
The phenomenon of cell cannibalism, which generally refers to the engulfment of Cells within other cells, was described in malignant tumors, but its biological significance is still largely unknown. in the present study, we investigated the occurrence, the in vivo relevance, and the underlying mechanisms of cannibalism in human melanoma. As first evidence, we observed that tumor cannibalism was clearly detectable in vivo in metastatic lesions of melanoma and often involved T cells, which could be found in a degraded state within tumor cells. Then, in vitro experiments confirmed that cannibalism of T cells was a property of metastatic melanoma cells but not. of primary melanoma cells. In particular, morphologic analyses, including time-lapse cinematography and electron microscopy, revealed a sequence of events, in which metastatic melanoma cells, were able to engulf and digest live autologous melanoma-specific CD8(+) T cells. Importantly, this cannibalistic activity significantly increased metastatic melanoma cell survival, particularly under starvation condition, supporting the evidence that tumor cells may use the eating of live lymphocytes as a way to "feed" in condition of low nutrient supply. The mechanism underlying cannibalism involved a complex framework, including lysosomal protease cathepsin 13 activity, caveolae formation, and ezrin cytoskeleton integrity and function. In conclusion, our study shows that human metastatic melanoma cells may cat live T cells, which are instead programmed to kill them, suggesting it novel mechanism of tumor immune escape. Moreover, our data suggest that cannibalism may represent a sort of "feeding" activity aimed at sustaining survival and progression of malignant tumor cells in an unfavorable microenvironment.