Sarosiek Konrad, Jones Elizabeth, Chipitsyna Galina, Al-Zoubi Mazhar, Kang Christopher, Saxena Shivam, Gandhi Ankit V, Sendiky Jocelyn, Yeo Charles J, Arafat Hwyda A
Department of Surgery, Jefferson Pancreatic, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
J Gastrointest Surg. 2015 Apr;19(4):639-50. doi: 10.1007/s11605-014-2735-6. Epub 2015 Jan 13.
Alternative splicing of osteopontin (OPN) produces three isoforms: OPNa, OPNb, and OPNc. The aims of this study were to examine the expression profile of OPN isoforms in sera from patients with pancreatic lesions and to determine their correlation with the presence of comorbid systemic inflammatory conditions, such as diabetes and/or obesity. Sera from 90 patients undergoing pancreatic surgery and 29 healthy volunteers were analyzed. Seventeen patients were diabetics, 17 were obese, and 6 had both diabetes and obesity. In patients with pancreatic lesions, OPNb was expressed in 48% of the patients' sera, OPNc in 34%, and both in 5%. The presence of diabetes and/or obesity was associated with complete disappearance of OPNb and expression of only OPNc. OPNc presence was significantly associated with diabetes and obesity (OR = 7.06 [95% CI 1.97-23.3]; p = 0.003). No OPNb or OPNc was detected in the normal sera. Overexpression of OPNb and OPNc isoforms in PDA cells significantly (p < 0.05) increased their activity in soft-agar colony formation and wound healing assays, induced the transcription of interleukin (IL)-6, and reduced tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and IL-10. Our data show for the first time the significant association between serum OPNc and diabetes and/or obesity. Unraveling the functional role of OPN isoforms in systemic inflammation is essential to understanding their significance as therapeutic targets in diabetes and obesity, and during metastasis development in PDA.
骨桥蛋白（OPN）的可变剪接产生三种异构体：OPNa、OPNb和OPNc。本研究的目的是检测胰腺病变患者血清中OPN异构体的表达谱，并确定它们与糖尿病和/或肥胖等合并全身性炎症性疾病的相关性。分析了90例接受胰腺手术患者和29名健康志愿者的血清。17例患者患有糖尿病，17例肥胖，6例同时患有糖尿病和肥胖。在胰腺病变患者中，48%的患者血清中表达OPNb，34%表达OPNc，5%同时表达两者。糖尿病和/或肥胖的存在与OPNb完全消失及仅OPNc表达相关。OPNc的存在与糖尿病和肥胖显著相关（OR = 7.06 [95% CI 1.97 - 23.3]；p = 0.003）。正常血清中未检测到OPNb或OPNc。PDA细胞中OPNb和OPNc异构体的过表达显著（p < 0.05）增加了它们在软琼脂集落形成和伤口愈合试验中的活性，诱导了白细胞介素（IL）-6的转录，并降低了肿瘤坏死因子α（TNF-α）、干扰素γ（IFN-γ）和IL-10。我们的数据首次表明血清OPNc与糖尿病和/或肥胖之间存在显著关联。阐明OPN异构体在全身性炎症中的功能作用对于理解它们作为糖尿病和肥胖治疗靶点以及在PDA转移发展过程中的意义至关重要。
