G蛋白偶聯(lián)受體（GPCRs）控制重要的生理過(guò)程,，一旦其功能發(fā)生障礙后會(huì)出現(xiàn)各種疾病包括癌癥,。孤兒G蛋白偶聯(lián)受體GPR55十多年前就已經(jīng)被發(fā)現(xiàn)確定,，但關(guān)于其與生理病理的相關(guān)作用卻一直了解不多,。
最近表明GPR55控制體外培養(yǎng)和異種移植的人癌癥細(xì)胞株的生物學(xué)行為,。然而,，有關(guān)這種受體在體內(nèi)惡變的實(shí)際作用的研究因?yàn)槿狈εR床相關(guān)模型而一再受到阻擾,。近日Oncogene雜志上的一則研究證實(shí)GPR55驅(qū)動(dòng)小鼠皮膚腫瘤的發(fā)展,。GPR55基因缺陷小鼠比野生型老鼠更能抵抗DMBA/TPA誘導(dǎo)的乳頭狀瘤的形成。GPR55的促腫瘤作用主要是由于其對(duì)癌細(xì)胞的增殖優(yōu)勢(shì),。
此外,，GPR55能增強(qiáng)皮膚癌細(xì)胞的錨定獨(dú)立生長(zhǎng)、侵襲和體內(nèi)致瘤能力,，這表明它不僅促進(jìn)腫瘤的發(fā)展,，而且對(duì)腫瘤的侵襲也至關(guān)重要。最后研究還發(fā)現(xiàn)相比于健康組織,，GPR55在人皮膚腫瘤和其他人鱗狀細(xì)胞癌中都存在相應(yīng)的表達(dá)上調(diào),。
總之，這些研究結(jié)果表明GPR55在皮膚腫瘤的發(fā)生發(fā)展中具有至關(guān)重要的意義,，這種受體可以作為一種新的生物標(biāo)志物來(lái)診斷治療鱗狀細(xì)胞癌,。（生物谷：Bioon.com）
doi:10.1038/onc.2012.278
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The orphan receptor GPR55 drives skin carcinogenesis and is upregulated in human squamous cell carcinomas.
Pérez-Gómez E, Andradas C, Flores JM, Quintanilla M, Paramio JM, Guzmán M, Sánchez C.
G protein-coupled receptors (GPCRs) control crucial physiological processes and their dysfunction contributes to various human diseases, including cancer. The orphan GPCR GPR55 was identified and cloned more than a decade ago, but very little is known about its physio-pathological relevance. It has been recently shown that GPR55 controls the behavior of human cancer cell lines in culture and xenografts. However, the assessment of the actual role of this receptor in malignant transformation in vivo is hampered by the lack of studies on its functional impact in clinically-relevant models of cancer. Here we demonstrate that GPR55 drives mouse skin tumor development. Thus, GPR55-deficient mice were more resistant to DMBA/TPA-induced papilloma and carcinoma formation than their wild-type littermates. GPR55 exerted this pro-tumor effect primarily by conferring a proliferative advantage on cancer cells. In addition, GPR55 enhanced skin cancer cell anchorage-independent growth, invasiveness and tumorigenicity in vivo, suggesting that it promotes not only tumor development but also tumor aggressiveness. Finally, we observed that GPR55 is upregulated in human skin tumors and other human squamous cell carcinomas compared with the corresponding healthy tissues. Altogether, these findings reveal the pivotal importance of GPR55 in skin tumor development, and suggest that this receptor may be used as a new biomarker and therapeutic target in squamous cell carcinomas.
