Department of Surgery and Institute for Research of Digestive System, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Int J Oncol. 2014 Jan;44(1):99-104. doi: 10.3892/ijo.2013.2156. Epub 2013 Oct 31.
Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind to the immunoreceptor NKG2D and play an important role in mediating cytotoxicity of NK and T cells. Release of MIC molecules from the cell surface is thought to constitute an immune escape mechanism of tumor cells and thus could be associated with more aggressive course of tumor growth. In this study, we investigated the expression of MICA/B in ductal pancreatic carcinoma and serum in relation to tumor stage, differentiation and survival. MICA/B expression in tumor tissues and sera from patients with pancreatic cancer were analyzed by immunohistochemical staining (IHC), western blotting and ELISA, respectively. MICA/B expression was present in 17 of 22 (77%) of the tumors but not in normal pancreatic ductal epithelial cells. Poorly differentiated tumors showed more pronounced MICA/B expression compared to differentiated tumors, but did not correlate significantly to other tumor characteristics. MICA/B-negative tumors displayed significantly lower incidence of lymph node metastases (p<0.01), and less mortality within 3 years following resection (p<0.02). In conclusion, tissue levels of MICA/B expression were elevated in pancreatic cancer cells without elevated levels in serum, despite well-recognized acute phase reactants in serum. Poorly differentiated tumors showed high MICA/B expression, which was related to extended tumor lymph node metastases and less frequent long-term survival.
主要组织相容性复合体Ⅰ类相关链 A 和 B（MICA/B）是两种应激诱导配体，与免疫受体 NKG2D 结合，在介导 NK 和 T 细胞细胞毒性方面发挥重要作用。MIC 分子从细胞表面释放被认为是肿瘤细胞的免疫逃逸机制，因此可能与肿瘤生长更具侵袭性的过程有关。在这项研究中，我们研究了 MICA/B 在导管腺癌和血清中的表达与肿瘤分期、分化和生存的关系。通过免疫组织化学染色（IHC）、western blot 和 ELISA 分别分析了胰腺癌患者肿瘤组织和血清中的 MICA/B 表达。在 22 例肿瘤中的 17 例（77%）中存在 MICA/B 表达，但在正常胰腺导管上皮细胞中不存在。与分化良好的肿瘤相比，分化不良的肿瘤表现出更明显的 MICA/B 表达，但与其他肿瘤特征无显著相关性。MICA/B 阴性肿瘤的淋巴结转移发生率显著降低（p<0.01），且术后 3 年内死亡率显著降低（p<0.02）。总之，尽管血清中存在公认的急性期反应物，但胰腺癌细胞中的 MICA/B 组织水平升高，而血清水平升高。分化不良的肿瘤表现出高 MICA/B 表达，与肿瘤淋巴结转移扩展和长期生存频率降低有关。
