Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, PR China.
Oncol Rep. 2012 Jul;28(1):262-8. doi: 10.3892/or.2012.1790. Epub 2012 Apr 26.
We investigated the expression of the co-signalling molecule CD40 in pancreatic cancer and the growth inhibitory effect of the recombinant soluble human CD40 ligand (rshCD40L) in pancreatic cancer cell lines. Twenty-six cases of pancreatic cancer tissues and corresponding paratumoral normal tissues were immunohistochemically analyzed for CD40 expression. The association of CD40 expression with clinicopathological parameters, including clinical stage, pathological grade, invasion and metastasis, were statistically analyzed. The serum sCD40 levels in pancreatic cancer patients were examined by ELISA. The expression of CD40 in the pancreatic cancer cell lines Panc-1, Aspc-1 and Miapaca-2 was examined by RT-PCR and flow cytometry. The growth inhibitory activity of rshCD40L on pancreatic cancer cell lines was determined by MTT assay. Tumor cell apoptosis was detected by TUNEL and Annexin V/PI double staining method. CD40 was positive both on the membrane and in the cytoplasm of tumor cells, 69.2% (18/26) of the cases were positive for CD40. CD40 expression was significantly higher in pancreatic cancer tissues compared to adjacent normal tissues (P<0.05). High CD40 expression was associated with TNM stage and lymph node metastasis (both P<0.05). Patients with pancreatic cancer have higher serum sCD40L levels (3.53 ± 0.70 ng/ml) compared to healthy subjects (1.81 ± 0.48 ng/ml, P<0.05). rshCD40L significantly inhibited the proliferation of the pancreatic cancer cell lines and induced apoptosis in these cell lines. The co-signaling molecule CD40 is highly expressed in pancreatic cancer tissues and cell lines and rshCD40L is a potential tool for antitumor therapies.
我们研究了共刺激分子 CD40 在胰腺癌中的表达以及重组可溶性人 CD40 配体（rshCD40L）对胰腺癌细胞系的生长抑制作用。采用免疫组织化学方法分析了 26 例胰腺癌组织和相应的癌旁正常组织中 CD40 的表达。统计分析了 CD40 表达与临床病理参数（包括临床分期、病理分级、浸润和转移）的相关性。采用 ELISA 法检测了胰腺癌患者血清中 sCD40 的水平。采用 RT-PCR 和流式细胞术检测了胰腺癌细胞系 Panc-1、Aspc-1 和 Miapaca-2 中 CD40 的表达。MTT 法检测了 rshCD40L 对胰腺癌细胞系的生长抑制活性。采用 TUNEL 和 Annexin V/PI 双染法检测肿瘤细胞凋亡。CD40 阳性定位于肿瘤细胞膜和细胞质，26 例病例中有 69.2%（18/26）为 CD40 阳性。胰腺癌组织中 CD40 的表达明显高于癌旁正常组织（P<0.05）。CD40 表达与 TNM 分期和淋巴结转移相关（均 P<0.05）。胰腺癌患者血清 sCD40L 水平（3.53±0.70 ng/ml）高于健康对照者（1.81±0.48 ng/ml，P<0.05）。rshCD40L 显著抑制了胰腺癌细胞系的增殖并诱导了这些细胞系的凋亡。共刺激分子 CD40 在胰腺癌组织和细胞系中高表达，rshCD40L 是一种有潜力的抗肿瘤治疗工具。
