El Fitori Jamael, Kleeff Jörg, Giese Nathalia A, Guweidhi Ahmed, Bosserhoff Anja K, Büchler Markus W, Friess Helmut
Department of General Surgery, University of Heidelberg, Germany.
Cancer Cell Int. 2005 Feb 14;5(1):3. doi: 10.1186/1475-2867-5-3.
Melanoma inhibitory activity (MIA) is a small secreted protein that interacts with extracellular matrix proteins. Its over-expression promotes the metastatic behavior of malignant melanoma, thus making it a potential prognostic marker in this disease. In the present study, the expression and functional role of MIA was analyzed in pancreatic cancer by quantitative real-time PCR (QRT-PCR), immunohistochemistry, immunoblot analysis and ELISA. To determine the effects of MIA on tumor cell growth and invasion, MTT cell growth assays and modified Boyden chamber invasion assays were used. RESULTS: The mRNA expression of MIA was 42-fold increased in pancreatic cancers in comparison to normal pancreatic tissues (p < 0.01). In contrast, MIA serum levels were not significantly different between healthy donors and pancreatic cancer patients. In pancreatic tissues, MIA was predominantly localized in malignant cells and in tubular complexes of cancer specimens, whereas normal ductal cells, acinar cells and islets were devoid of MIA immunoreactivity. MIA significantly promoted the invasiveness of cultured pancreatic cancer cells without influencing cell proliferation. CONCLUSION: MIA is over-expressed in pancreatic cancer and has the potential of promoting the invasiveness of pancreatic cancer cells.
黑色素瘤抑制活性蛋白(MIA)是一种与细胞外基质蛋白相互作用的小分泌蛋白。其过度表达促进恶性黑色素瘤的转移行为,因此使其成为该疾病潜在的预后标志物。在本研究中,通过定量实时聚合酶链反应(QRT-PCR)、免疫组织化学、免疫印迹分析和酶联免疫吸附测定(ELISA)对胰腺癌中MIA的表达及其功能作用进行了分析。为了确定MIA对肿瘤细胞生长和侵袭的影响,采用了MTT细胞生长试验和改良的博伊登小室侵袭试验。结果:与正常胰腺组织相比,胰腺癌中MIA的mRNA表达增加了42倍(p < 0.01)。相比之下,健康供体和胰腺癌患者之间的MIA血清水平无显著差异。在胰腺组织中,MIA主要定位于恶性细胞和癌组织标本的管状复合体中,而正常导管细胞、腺泡细胞和胰岛均无MIA免疫反应性。MIA显著促进培养的胰腺癌细胞的侵袭性,但不影响细胞增殖。结论:MIA在胰腺癌中过度表达,具有促进胰腺癌细胞侵袭的潜力。