Zhou Hong, Hu Hongxin, Shi Wenxia, Ling Shucai, Wang Ting, Wang Haibo
Department of Clinical Laboratory and Hematology, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
Oncol Rep. 2008 Nov;20(5):1069-76.
Tissue factor (TF) is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Protease-activated receptors (PARs) are widely expressed on various cells including tumor cells and associated with many pathological mechanisms. In the present study, the expression of TF and PAR1, PAR2 on human colon cancer cells (SW620 and SW480) was investigated and their functional roles on the behavior of tumor cells were evaluated. It was demonstrated that SW620 and SW480 cells expressed TF at antigen, activity and mRNA levels. However, the highly metastatic cell line SW620 showed slightly higher TF expression than the low metastatic cell line SW480. The PAR2 antigen was strongly expressed on the membrane of SW620 cells, but not on SW480 cells. The PAR1 antigen was not observed in SW620 or SW480 cells, while PAR1 and PAR2 mRNA was detected in SW620 and SW480 cells. The migratory potential of SW620 was stronger than that of SW480 seen in Boyden chambers. PAR2 agonist (SLIGKV-NH2) and factor VIIa significantly stimulated SW620 cell proliferation, migratory activity, and interleukin 8 (IL-8) secretion compared to control. The stimulating effects of factor VIIa could be inhibited by anti-TF and anti-PAR2 but not anti-PAR1 antibodies. In summary, this study demonstrates that TF and PAR2 are strongly expressed on highly metastatic colonic tumor cells and are closely associated with the proliferation and migration of the cells. TF may elucidate its roles in colonic cancer invasion and metastasis via PAR2 pathway.
组织因子（TF）被认为在组织修复、炎症、血管生成和肿瘤转移中发挥重要作用。蛋白酶激活受体（PARs）在包括肿瘤细胞在内的各种细胞上广泛表达，并与许多病理机制相关。在本研究中，研究了TF以及PAR1、PAR2在人结肠癌细胞（SW620和SW480）上的表达情况，并评估了它们在肿瘤细胞行为中的功能作用。结果表明，SW620和SW480细胞在抗原、活性和mRNA水平上均表达TF。然而，高转移细胞系SW620的TF表达略高于低转移细胞系SW480。PAR2抗原在SW620细胞膜上强烈表达，但在SW480细胞上不表达。在SW620或SW480细胞中未观察到PAR1抗原，而在SW620和SW480细胞中检测到PAR1和PAR2 mRNA。在Boyden小室中，SW620的迁移潜力强于SW480。与对照组相比，PAR2激动剂（SLIGKV-NH2）和凝血因子VIIa显著刺激SW620细胞增殖、迁移活性和白细胞介素8（IL-8）分泌。凝血因子VIIa的刺激作用可被抗TF和抗PAR2抗体抑制，但不能被抗PAR1抗体抑制。总之，本研究表明TF和PAR2在高转移性结肠肿瘤细胞上强烈表达，并与细胞的增殖和迁移密切相关。TF可能通过PAR2途径在结肠癌侵袭和转移中发挥作用。
