骨桥蛋白及CD44v6在肺腺癌侵袭转移中的作用

Effect of osteopontin and CD44v6 in the progression of lung adenocarcinoma

目的探讨骨桥蛋白(OPN)及其受体CD44v6在肺腺癌侵袭转移中的作用。方法应用免疫组化方法检测129例癌旁组织、肺原位腺癌(AIS)、伏壁样生长为主型腺癌(LPA)患者手术切除标本中OPN、CD44v6的表达情况。检测H358细胞(原位癌细胞系)和A549细胞中OPN、CD44v6蛋白及mRNA的表达,Transwell试验观察OPN、CD44v6对H358细胞、A549细胞侵袭力的影响。结果 OPN、CD44v6在LPA组织中的表达阳性率显著高于AIS及癌旁组织,AIS高于癌旁组织,OPN与CD44v6的表达呈显著正相关(P<0.05)。OPN、CD44v6及OPN mRNA、CD44v6 mRNA在A549细胞中的表达水平高于H358细胞。Transwell试验提示OPN对A549细胞的趋化作用高于H358细胞。使用OPN抗体阻断OPN对两种细胞的趋化作用,两种细胞穿过数均减少;阻断CD44v6受体通道后,OPN对两种细胞的趋化作用明显减弱。结论 OPN-CD44v6复合体对肺腺癌的侵袭能力具有重要作用,OPN有望成为评估肺腺癌进展及预测肿瘤转移潜能的指标。

Objective To investigate the role of OPN and CD44v6 in the progression and invasion of lung adenocarci-noma.Methods OPN and CD44v6 expressions were detected in 129 patients with pericarcinomatous tissue , lung adeno-carcinoma in situ （ AIS ） and lepidic predominant adenocarcinoma （ LPA ） by immunohistochemical method .OPN and CD44v6 expressions were detected in H358 cells （lung adenocarcinoma in situ cell line ） and A549 cells by Western blot. Quantitative PCR was used to determine the expression levels of OPN mRNA and CD 44v6 mRNA.The influence of OPN and CD44 v6 on the invasive ability of H 358 cells and A549 cells was examined by Transwell chamber assay .Results Im-munohistochemical method revealed that the positive expression rates of OPN and CD 44v6 in LPA were significantly higher than those in AIS and pericarcinomatous tissue;the positive rates were higher in AIS compared to pericarcinomatous tissue . The expressions of these two markers were correlated positively （P〈0.05）.Western blot revealed that the positive expres-sion rates of OPN and CD44v6 in A549 cells were higher than those in H358 cells.Quantitative PCR revealed that the ex-pression levels of OPN and CD44v6 in A549 cells were higher than those in H358 cells.Transwell chamber assay revealed that OPN induced chemotaxis of cancer cells , and the chemotaxis was higher in A 549 cells than that in H358 cells.The mi-gration cell numbers of the two kinds of cancer cells decreased when blocked by OPN antibody .When the CD44 v6 receptor channel was blocked , OPN＆#39;s chemotactic effect was weakened .Conclusion The OPN-CD44v6 complex plays an important role in lung adenocarcinoma progression;OPN might be used as an indicator to predict the progression and metastatic poten-tial of lung adenocarcinoma .