Pottratz S T, Hall T D, Scribner W M, Jayaram H N, Natarajan V
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202, USA.
Am J Physiol. 1996 Dec;271(6 Pt 1):L918-23. doi: 10.1152/ajplung.1996.271.6.L918.
Small cell lung carcinoma (SCLC) frequently metastasizes early in the course of the disease. P-selectin (P-sel), a cell adhesion molecule expressed on activated platelets and endothelial cells (EC), has previously been demonstrated to mediate binding of platelets to SCLC. We hypothesized that P-sel facilitates attachment of SCLC to EC, acting as an important factor in SCLC metastasis. To test this hypothesis, attachment of H82 cells (SCLC cell line) to EC was quantified. Attachment of H82 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated EC was increased compared with control EC. Increased attachment of H82 cells to EC was apparent after 10 min of TPA activation, reached a peak after 30 min, and returned to baseline after 120 min of exposure. The TPA-induced increase in H82 cell attachment to EC was inhibited by addition of anti-P-sel antibodies but not by addition of anti-E-selectin antibodies. The TPA-induced increase in H82 cell attachment was likely mediated by activation of EC protein kinase C (PKC). Pretreatment of the EC with PKC inhibitors effectively blocked the TPA-mediated increase in H82 cell attachment. In addition, prolonged exposure of EC to TPA resulted in decreased expression of the PKC-alpha and PKC-epsilon isoforms. These data indicate for the first time that attachment of SCLC to activated EC appears to be mediated by increased expression of P-sel on the EC surface, which may result from activation of specific isoforms of PKC.
小细胞肺癌（SCLC）在疾病进程中常常早期发生转移。P-选择素（P-sel）是一种在活化血小板和内皮细胞（EC）上表达的细胞粘附分子，先前已证明其介导血小板与SCLC的结合。我们推测P-sel促进SCLC与EC的附着，是SCLC转移中的一个重要因素。为了验证这一假设，对H82细胞（SCLC细胞系）与EC的附着情况进行了定量分析。与对照EC相比，H82细胞与12-O-十四酰佛波醇-13-乙酸酯（TPA）活化的EC的附着增加。TPA活化10分钟后，H82细胞与EC的附着增加明显，30分钟后达到峰值，暴露120分钟后恢复到基线水平。添加抗P-sel抗体可抑制TPA诱导的H82细胞与EC附着的增加，但添加抗E-选择素抗体则无此作用。TPA诱导的H82细胞附着增加可能是由EC蛋白激酶C（PKC）的激活介导的。用PKC抑制剂预处理EC可有效阻断TPA介导的H82细胞附着增加。此外，EC长时间暴露于TPA会导致PKC-α和PKC-ε同工型的表达降低。这些数据首次表明，SCLC与活化EC的附着似乎是由EC表面P-sel表达增加介导的，这可能是由PKC特定同工型的激活所致。
