Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples
Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples
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DOI：
10.1002/ijc.20607
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发表时间：
2005-01-20
影响因子：
6.4
通讯作者：
Bar-Shavit, R
中科院分区：
文献类型：
--
作者：
Grisaru-Granovsky, S;Salah, Z;Bar-Shavit, R
蛋白酶激活受体（PAR）是一个由G蛋白偶联受体（GPCR）组成的家族，它编码自身的配体，并通过蛋白水解裂解而被激活。虽然蛋白酶一般已被牵连在细胞外肿瘤微环境的重塑，蛋白水解激活的细胞表面受体的作用，现在正在出现。在我们目前的研究中，我们研究了蛋白酶激活受体I hPar 1在卵巢癌组织样本中的表达模式。丰富的hPar 1 mRNA和蛋白质检测“低恶性潜能”和浸润性癌，无论组织学亚型。相反，在正常卵巢上皮细胞表面没有检测到hPar 1的表达。原位杂交、免疫组化和半定量RT-PCR分析显示hPar 1的差异表达模式。在卵巢癌（Ia）的早期阶段，对侧正常卵巢显示出强PAR 1表达，而在正常个体的卵巢上皮中缺乏表达。同时，我们分析了这些组织中α v β 5整合素和活化的粘着斑激酶（FAK）（一种主要的局灶性接触蛋白）的表达模式。尽管在所有检查的组织样本中观察到α v β 5整合素的丰富表达，无论是正常的还是恶性的，活化的FAK的水平都是差异表达的。磷酸化FAK在浸润性卵巢癌中表达，而在正常卵巢上皮中未见表达。病理性恶性卵巢癌中丰富的hPar 1水平可能传递导致FAK磷酸化的信号，从而改变整合素功能状态。总之，我们的数据表明，hPar 1和FAK合作，促进卵巢癌恶性。
Protease activated receptors (PAR) form a family of G-protein coupled receptors (GPCR) encoding their own ligands and uniquely activated via proteolytic cleavage. Although proteases in general have been implicated in the remodeling of the extracellular tumor microenvironment, the role of cell surface receptors activated by proteolysis is now emerging. In our present study we investigated the expression pattern of protease activated receptor I hPar1 in ovarian carcinoma tissue samples. Abundant hPar1 mRNA and protein were detected in "low malignant potential" and in invasive carcinomas, regardless of the histological subtype. In contrast, no hPar1 expression was detected on the cell surface of normal ovarian epithelium. The differential expression pattern of hPar1 was shown by in situ hybridization, immunohistochemistry and semi-quantitative RT-PCR analyses. In early stages of ovarian carcinoma (Ia), the contra lateral normal ovary showed strong PAR1 expression as opposed to the lack of expression in the ovarian epithelium obtained from normal individuals. In parallel, we analyzed the expression pattern of alphavbeta5 integrin and of activated focal adhesion kinase (FAK), a major focal contact protein, in these tissues. Although abundant expression of alphavbeta5 integrin was observed in all tissues specimens examined, regardless of either normal or malignant, the level of activated FAK was differentially expressed. Phosphorylated FAK was seen in invasive ovarian carcinoma, but not in the normal ovarian epithelium. The abundant hPar1 levels in pathological malignant ovarian carcinoma is likely to transmit signals leading to the phosphorylation of FAK and thereby alterations in the integrin functional state. Altogether our data suggest that hPar1 and FAK cooperate to promote ovarian cancer malignancy.