Department of Clinical Laboratory and Hematology, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, PR China.
Oncol Rep. 2011 Feb;25(2):503-11. doi: 10.3892/or.2010.1077. Epub 2010 Dec 7.
Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor and its activation has been associated with the pathogenetic progress in certain cancers. Toll-like receptor 4 (TLR4), one member of Toll-like receptors family, is mainly contributed to the innate immune response. However, recent studies have shown that TLR4 is aberrantly expressed in various types of carcinomas and may correlate with tumor progression. Previously, we reported that PAR2 could be expressed in human colon cancer cell line (SW620) and its activation by some stimulants was able to facilitate cell proliferation and migration. In our recent preliminary experiment, it was found that SW620 cells also had TLR4 expression. Thus, we considered that PAR2 and TLR4 could have some collaborative roles in SW620 cells. In the current study, the cross-inducible expression of PAR2 and TLR4 on SW620 cells was investigated, and the functional roles of their activation on the behavior of SW620 cells were evaluated. It was found that activation of PAR2 with PAR2-AP (PAR2 agonist, 100 μM) enhanced TLR4 releasement and vice versa. The activation of PAR2 or TLR4 (with LPS, 100 ng/ml) could promote SW620 cell proliferation and migration, and the phosphorylation of ERK1/2 but not p38MAPK, as well as the expression of interleukin 8 (IL-8) and tissue factor (TF). Whereas the caspase-7 expression was decreased under PAR2 or TLR4 activation. Furthermore, ERK1/2 inhibitor (U0126, at 10 μM) could intervene in all regulating effects of PAR2 or/and TLR4. Collectively, this study demonstrated that both PAR2 and TLR4 activation on SW620 cells can trigger the phosphorylation of ERK1/2, regulate the expression of IL-8, TF and caspase-7, thereby promote the proliferation and migration of cells.
蛋白酶激活受体 2 (PAR2) 是一种 G 蛋白偶联受体，其激活与某些癌症的发病机制进展有关。Toll 样受体 4 (TLR4) 是 Toll 样受体家族的成员之一，主要参与固有免疫反应。然而，最近的研究表明，TLR4 在各种类型的癌中异常表达，并且可能与肿瘤的进展相关。之前，我们报道 PAR2 可以在人结肠癌细胞系 (SW620) 中表达，其被某些刺激物激活后能够促进细胞增殖和迁移。在我们最近的初步实验中，发现 SW620 细胞也表达 TLR4。因此，我们认为 PAR2 和 TLR4 在 SW620 细胞中可能具有某些协同作用。在本研究中，研究了 SW620 细胞中 PAR2 和 TLR4 的交叉诱导表达，并评估了它们的激活对 SW620 细胞行为的功能作用。结果发现，用 PAR2-AP（PAR2 激动剂，100 μM）激活 PAR2 增强了 TLR4 的释放，反之亦然。激活 PAR2 或 TLR4（用 LPS，100 ng/ml）可促进 SW620 细胞的增殖和迁移，以及 ERK1/2 的磷酸化，但不影响 p38MAPK，以及白细胞介素 8 (IL-8) 和组织因子 (TF) 的表达。然而，PAR2 或 TLR4 激活时 caspase-7 的表达减少。此外，ERK1/2 抑制剂 (U0126，10 μM) 可干预 PAR2 或/和 TLR4 的所有调节作用。总之，这项研究表明，SW620 细胞中 PAR2 和 TLR4 的激活均可触发 ERK1/2 的磷酸化，调节 IL-8、TF 和 caspase-7 的表达，从而促进细胞的增殖和迁移。
