GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis.
GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis.
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DOI：
10.1111/bph.13345
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发表时间：
2016-01
影响因子：
7.3
通讯作者：
Schicho R
中科院分区：
文献类型：
--
作者：
Kargl J;Andersen L;Hasenöhrl C;Feuersinger D;Stančić A;Fauland A;Magnes C;El-Heliebi A;Lax S;Uranitsch S;Haybaeck J;Heinemann A;Schicho R
肿瘤细胞的迁移和粘附构成转移的基本特征。G蛋白偶联受体55（GPR55）是一种溶血磷脂受体，在肿瘤发生中起重要作用。在这里，我们研究了GPR55参与结肠癌细胞的迁移和转移。使用高转移性结肠癌细胞系HCT 116进行粘附和迁移测定，并进行肝转移的体内测定。GPR55拮抗剂CID16020046、大麻二酚（一种推定的GPR55拮抗剂）和GPR55 siRNA用于阻断HCT 116结肠癌细胞中的GPR55活性。HCT116细胞在用CID16020046或大麻二酚阻断后显示出与内皮细胞的粘附和迁移的显著降低。CID16020046或大麻二酚的抑制作用通过GPR55 siRNA敲低在癌细胞中避免。用拮抗剂预处理HCT 116细胞或GPR55 siRNA敲低后，内皮细胞单层的完整性增加，而用GPR55的内源性配体溶血磷脂酰肌醇（LPI）预处理，单层的完整性降低。LPI还诱导GPR55过表达的HCT 116细胞的迁移，该迁移被GPR55拮抗剂阻断。在转移的小鼠模型中，用CID16020046或大麻二酚治疗后，肝脏中HCT 116癌细胞的停滞减少。与健康个体相比，结肠癌患者的LPI水平增加（18：0）。GPR55参与结肠癌细胞的迁移行为，并可能作为预防转移的药理学靶点。
Tumor cell migration and adhesion constitute essential features of metastasis. G protein-coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cancer cells. Adhesion and migration assays using the highly metastatic colon cancer cell line HCT116 and an in vivo assay of liver metastasis were performed. GPR55 antagonist CID16020046, cannabidiol, a putative GPR55 antagonist, and GPR55 siRNA were used to block GPR55 activity in HCT116 colon cancer cells. HCT116 cells showed a significant decrease in adhesion to endothelial cells and in migration after blockade with CID16020046 or cannabidiol. The inhibitory effects of CID16020046 or cannabidiol were averted by GPR55 siRNA knock down in cancer cells. The integrity of endothelial cell monolayers was increased after pretreatment of HCT116 cells with the antagonists or after GPR55 siRNA knockdown while pretreatment with lysophosphatidylinositol (LPI), the endogenous ligand of GPR55, decreased integrity of the monolayers. LPI also induced migration in GPR55 overexpressing HCT116 cells that was blocked by GPR55 antagonists. In a mouse model of metastasis, the arrest of HCT116 cancer cells in the liver was reduced after treatment with CID16020046 or cannabidiol. Increased levels of LPI (18:0) was found in colon cancer patients when compared to healthy individuals. GPR55 is involved in the migratory behavior of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis.