Koshiba T, Hosotani R, Miyamoto Y, Ida J, Tsuji S, Nakajima S, Kawaguchi M, Kobayashi H, Doi R, Hori T, Fujii N, Imamura M
Department of Surgery, Kyoto University, Japan.
Clin Cancer Res. 2000 Sep;6(9):3530-5.
To examine the expression of the stromal cell-derived factor 1 (SDF-1)/CXCR4 receptor ligand system in pancreatic cancer cells and endothelial cells, we performed immunohistochemical analysis for 52 pancreatic cancer tissue samples with anti-CXCR4 antibody and reverse transcription-PCR analysis for CXCR4 and SDF-1 in five pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, and PANC-1), an endothelial cell line (HUVEC), and eight pancreatic cancer tissues. We then performed cell migration assay on AsPC-1 cells, HUVECs, and CFPAC-1 cells in the presence of SDF-1 or MRC-9 fibroblast cells. Immunoreactive CXCR4 was found mainly in pancreatic cancer cells and endothelial cells of relatively large vessels around a tumorous lesion. The immunopositive ratio in the pancreatic cancer was 71.2%. There was no statistically significant correlation with clinicopathological features. SDF-1 mRNA expressions were detected in all pancreatic cancer tissues but not in pancreatic cancer cell lines and HUVECs; meanwhile, CXCR4 mRNA was detected in all pancreatic cancer tissues, cancer cell lines, and HUVECs. The results indicate that the paracrine mechanism is involved in the SDF-1/CXCR4 receptor ligand system in pancreatic cancer. In vitro studies demonstrated that SDF-1 significantly increased the migration ability of AsPC-1 and HUVECs, and these effects were inhibited by CXCR4 antagonist T22, and that the coculture system with MRC-9 also increased the migration ability of CFPAC-1 cells, and this effect was significantly inhibited by T22. Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in the pancreatic cancer progression through tumor cell migration and angiogenesis.
为检测基质细胞衍生因子1（SDF-1）/CXCR4受体配体系统在胰腺癌细胞和内皮细胞中的表达，我们用抗CXCR4抗体对52例胰腺癌组织样本进行了免疫组化分析，并对5种胰腺癌细胞系（AsPC-1、BxPC-3、CFPAC-1、HPAC和PANC-1）、1种内皮细胞系（HUVEC）以及8例胰腺癌组织中的CXCR4和SDF-1进行了逆转录-聚合酶链反应分析。然后，我们在SDF-1或MRC-9成纤维细胞存在的情况下，对AsPC-1细胞、HUVEC和CFPAC-1细胞进行了细胞迁移试验。免疫反应性CXCR4主要在肿瘤病变周围相对较大血管的胰腺癌细胞和内皮细胞中发现。胰腺癌中的免疫阳性率为71.2%。与临床病理特征无统计学显著相关性。在所有胰腺癌组织中均检测到SDF-1 mRNA表达，但在胰腺癌细胞系和HUVEC中未检测到；同时，在所有胰腺癌组织、癌细胞系和HUVEC中均检测到CXCR4 mRNA。结果表明旁分泌机制参与了胰腺癌中SDF-1/CXCR4受体配体系统。体外研究表明，SDF-1显著提高了AsPC-1和HUVEC的迁移能力，这些作用被CXCR4拮抗剂T22抑制，并且与MRC-9的共培养系统也提高了CFPAC-1细胞的迁移能力，且这种作用被T22显著抑制。我们的结果提示，SDF-1/CXCR4受体配体系统可能通过肿瘤细胞迁移和血管生成在胰腺癌进展中发挥作用。
