GPR56 and TG2 - Possible roles in suppression of tumor growth by the microenvironment
GPR56 and TG2 - Possible roles in suppression of tumor growth by the microenvironment
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DOI：
10.4161/cc.6.2.3760
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发表时间：
2007-01-15
期刊：
影响因子：
4.3
通讯作者：
Hynes, Richard O.
中科院分区：
文献类型：
--
作者：
Xu, Lei;Hynes, Richard O.
转移是一个复杂的过程，涉及多个层面的细胞 - 细胞相互作用。在这些相互作用中，肿瘤 - 基质相互作用正在被积极研究。据推测，转移细胞会出现基因表达变化，这些变化有助于它们在远处部位的存活和生长。这种变化可能要么促进生长，要么逃避正常组织环境的生长抑制，从而作为转移灶生长。我们最近的报告指出，来自高度转移性黑色素瘤衍生物的肿瘤表达低水平的肿瘤进展抑制因子GPR56，这与这样一个模型是相符的。GPR56与Gαq和四跨膜蛋白CD81形成复合物。我们进一步确定了一种在细胞外基质（ECM）中与GPR56相互作用的配体为TG2，它是基质中的一种主要交联酶。TG2还与纤连蛋白和整合素结合，并影响它们的细胞黏附功能。TG2本身已被认为与抑制肿瘤进展有关；因此，TG2可能作为一种针对入侵的转移细胞的宿主防御机制。高度转移性细胞可能通过下调GPR56逃避这种抑制。未来需要大量的工作来验证这一假设，并进一步加深我们对转移的总体理解。
Metastasis is a complex process that involves multiple levels of cell-cell interaction. Among these interactions, tumor-stroma interactions are being actively investigated. Metastatic cells are hypothesized to show gene expression changes that contribute to their survival and growth at the distant site. Such changes could contribute either to enhancement of growth or to evasion of growth inhibition by the normal tissue environment thus allowing growth as metastases. Our recent report that tumors from highly metastatic melanoma derivatives express low levels of a suppressor of tumor progression, GPR56, is consistent with such a model. GPR56 associates in a complex with G alpha q and the tetraspanin protein CD81. We further identified a ligand that interacts with GPR56 in the extracellular matrix (ECM) as TG2, a major crosslinking enzyme in the matrix. TG2 also binds to fibronectin and integrins and affects their cell adhesion functions. TG2 itself has been implicated in suppression of tumor progression; therefore TG2 might serve as a host defense against the invading metastatic cells. The highly metastatic cells may escape from this inhibition by down-regulation of GPR56. Much future work will be needed to test this hypothesis and further our understanding of metastasis in general.