半乳糖-3-O-磺酰基转移酶-2与肿瘤转移关系的研究

Correlation Between The Expression of Gal: 3-O-sulfotransferase-2 and Metastasis Potentials of Cancer Cells

半乳糖-3-O-磺酰基转移酶-2(GP3ST)是一个新近克隆的磺酰基转移酶,其生物学功能还不明确.GP3ST在肿瘤细胞和肿瘤组织中差异性表达,以及催化所形成的磺酰化糖链与肿瘤转移潜能密切相关,是首次研究报道.在高转移潜能的肿瘤细胞中,GP3ST及其产物的表达明显高于低转移潜能的细胞,在伴有淋巴结转移的喉癌组织中,GP3ST的高表达率也明显高于无淋巴结转移的喉癌组织(P<0.05),而且在喉癌组织中的表达也明显高于相对应的癌周组织.利用RNAi技术下调肝癌细胞SMMC7721中GP3ST的表达,观察到稳定转染RNAi/GP3ST的细胞形态发生明显的改变,由多边形转变为近似梭形,与TNF-α刺激后的HUVEC和sL-选凝蛋白的黏附能力下降.进一步研究表明,GP3ST表达的下降能抑制细胞中的整合蛋白αV亚基的表达,而β3亚基表达无改变,同时在高转移细胞株中αV的表达也明显高于低转移细胞株,与GP3ST表达的差异性相一致.上述结果充分说明GP3ST催化合成的糖链可通过调节肿瘤细胞的黏附性和影响整合蛋白αV亚基的表达参与肿瘤转移.

The Gal: 3-0-sulfotransferase-2 (GP3ST) was a newly cloned sulfotransferase and its biological significance remained unknown. The expression levels in different metastatic potential tumor cells and larynx cancer tissues were investigated. A significantly higher expression level of GP3ST and sulfated glycocojugates were observed in highly metastastic cancer cells and larynx cancer tissues with lymph node metastasis than those in lowly metastatic cancer cells and ones without metastasis (P < 0.05, n = 42). GP3 ST expression was further suppressed by targeted RNAi technology in hepatocarcinoma cells SMMC7721. It was found that the morphology of SMCC7721 cells transfected with RNAi-GP3ST was changed from polygon to shuttle shape and the adhesion ability to HUVEC induced by TNF-alpha and sL-selectin was significantly decreased. Furthermore, the decreased expression of GP3ST could lead to expression inhibition of integrin subunit alpha V, but didn't affect the expression of integrin subunit beta 3 by Western blot analysis and RT-PCR. The result of higher alpha V expression in high metastatic cells than in low metastatic cells was consistant with the differential expression of GP3ST. Taken together the results suggested that the expression of GP3ST may be involved in tumor metastasis process by regulation of adhesion ability and expression of integrin alpha V.