Department of Internal Medicine, Division of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Cancer. 2013 Jan 1;119(1):233-44. doi: 10.1002/cncr.27669. Epub 2012 Jun 26.
Tumor-derived soluble factors serve as mediators between tumors and surrounding microenvironment to promote tumor growth and metastasis under a complex network. The objective of this study was to evaluate the relationships between soluble major histocompatibility complex class I chain-related molecule A (sMICA) and 4 categories of cytokines (tumor-related proinflammatory, anti-inflammatory, chemotactic/proangiogenic, and growth-stimulatory) in the development and progression of pancreatic ductal adenocarcinoma (PDAC).
Serum levels of sMICA and 4-categorized cytokines were measured by enzyme-linked immunosorbent assay and chemiluminescent immunoassay, respectively, in 134 individuals (normal, n = 55; chronic pancreatitis, n = 25; PDAC, n = 54). Clinical implications of sMICA and tumor-related cytokines, their correlations, and diagnostic usefulness in PDAC were evaluated.
Serum sMICA, which was associated with the development and progression of PDAC, correlated with interferon-γ negatively (P = 0.024), whereas it correlated positively with the anti-inflammatory cytokines interleukin-10 (IL-10) and IL-1 receptor antagonist, and the bifunctional cytokine tumor necrosis factor α, with respect to PDAC development (P < .05). sMICA also correlated positively with the chemotactic/proangiogenic cytokines vascular endothelial growth factor, soluble CD40 ligand, and IL-8, and the tumor growth-stimulatory cytokines epidermal growth factor and transforming growth factor α, with respect to PDAC development and/or progression. Logistic regression analysis validated the diagnostic usefulness of combination use of sMICA and its related cytokines to predict the presence of PDAC and distant metastasis in PDAC, superior to carbohydrate antigen 19-9.
sMICA may be involved in tumor-associated angiogenesis and tumor growth either directly or indirectly by affecting corresponding cytokines as well as causing impairment of natural killer cell cytotoxicity in the development and progression of PDAC. A combination of sMICA and its related cytokines exhibited remarkable diagnostic potential in PDAC.
肿瘤衍生的可溶性因子作为肿瘤与周围微环境之间的介质，在复杂的网络中促进肿瘤生长和转移。本研究的目的是评估可溶性主要组织相容性复合体 I 类相关分子 A（sMICA）与 4 类细胞因子（肿瘤相关促炎、抗炎、趋化/血管生成和生长刺激）之间的关系在胰腺导管腺癌（PDAC）的发生和发展中的作用。
采用酶联免疫吸附试验和化学发光免疫分析法分别检测 134 例个体（正常对照 55 例、慢性胰腺炎 25 例、PDAC 54 例）血清 sMICA 和 4 分类细胞因子水平。评估 sMICA 和肿瘤相关细胞因子的临床意义、相关性及其在 PDAC 中的诊断价值。
与 PDAC 发生和发展相关的血清 sMICA 与干扰素-γ呈负相关（P=0.024），而与抗炎细胞因子白细胞介素-10（IL-10）和白细胞介素-1 受体拮抗剂以及双功能细胞因子肿瘤坏死因子-α呈正相关，与 PDAC 发生相关（P<.05）。sMICA 还与趋化/血管生成细胞因子血管内皮生长因子、可溶性 CD40 配体和白细胞介素-8 以及肿瘤生长刺激细胞因子表皮生长因子和转化生长因子-α呈正相关，与 PDAC 的发生和/或进展相关。Logistic 回归分析验证了 sMICA 及其相关细胞因子联合使用预测 PDAC 存在和 PDAC 远处转移的诊断价值，优于糖链抗原 19-9。
sMICA 可能通过影响相应的细胞因子，直接或间接参与肿瘤相关的血管生成和肿瘤生长，导致自然杀伤细胞细胞毒性受损，从而在 PDAC 的发生和发展中发挥作用。sMICA 及其相关细胞因子的联合具有显著的 PDAC 诊断潜力。
