胃幽門螺旋桿菌之熱緊迫蛋白60藉由活化CXCR2訊息路徑而增加血管新生

Abstract

胃幽門螺旋桿菌已知為可造成胃癌的微生物，此菌之熱緊迫蛋白60可誘發發炎反應。本篇研究目的在於探討熱緊迫蛋白60在胃癌發展所扮演的角色。首先，我們發現在病人血清中的抗熱緊迫蛋白60抗體的表現與癌症有正向的關聯, 從此發現我們推測此蛋白與癌症有關，因此我們進一步的探討熱緊迫蛋白60在細胞增生、抗凋亡、血管新生、轉移能力之能力。研究結果顯示熱緊迫蛋白60可促進胃癌細胞之血管新生與細胞遷移，但不幫助胃癌細胞之增生與抗凋亡能力。此外，研究結果也顯示熱緊迫蛋白60能刺激單核球細胞株THP1、胃癌細胞株AGS、人類臍靜脈內皮細胞分泌血管新生因子，並且可促進人類臍靜脈內皮細胞三維血管生成、細胞遷移、間接促進內皮細胞增生。另外，以抑制劑抑制CXCR2訊息路徑可抑制熱緊迫蛋白60誘發之三維血管生成。因此，從這些結果我們推測胃幽門螺旋桿菌之熱緊迫蛋白可刺激血管新生因子分泌並且藉由CXCR2訊息路徑來促進血管新生。

Helicobacter pylori, the microbe has been discovered it can promote the malignant process of gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previous identified as a potent immunogen. This study aims to study the role of HpHSP60 on gastric cancer carcinogenesis. First, the results of patients’ anti-HpHSP60 antibodies in sera were correlated to gastric cancer. According to these finding, this pathogen-derived component was speculated it may play a role in tumor malignant process. Sequentially, we investigated the effect of HpHsp60 on the cell proliferation, anti-death activities, angiogenesis, and metastasis. The results showed HpHSP60 could enhance migration of gastric cancer cells and promote angiogenesis it had no effect on proliferation and rescuing cell death of gastric cancer cells. Moreover, the results showed HpHSP60 could stimulate THP1 monocytic cells, AGS gastric cancer cells, and umbilical vein endothelial cells (HUVECs) to express the angiogeneic factors. In addition, HpHSP60 could also enhance tube formation, migration and indirectly promote proliferation of HUVECs. Furthermore, inhibition of CXCR2 signal decreased the tube formation. Therefore, these results propose HpHSP60 may trigger angiogeneic factor releases and enhance the angiogenesis via CXCR2-dependent pathway.