Suzuki Hiroyuki, Kato Yukinari, Kaneko Mika Kato, Okita Yukari, Narimatsu Hisashi, Kato Mitsuyasu
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
FEBS Lett. 2008 Jan 23;582(2):341-5. doi: 10.1016/j.febslet.2007.12.028. Epub 2007 Dec 26.
Podoplanin/aggrus is increased in tumors and its expression was associated with tumor malignancy. Podoplanin on cancer cells serves as a platelet-aggregating factor, which is associated with the metastatic potential. However, regulators of podoplanin remain to be determined. Transforming growth factor-beta (TGF-beta) regulates many physiological events, including tumorigenesis. Here, we found that TGF-beta induced podoplanin in human fibrosarcoma HT1080 cells and enhanced the platelet-aggregating-ability of HT1080. TGF-beta type I receptor inhibitor (SB431542) and short hairpin RNAs for Smad4 inhibited the podoplanin induction by TGF-beta. These results suggest that TGF-beta is a physiological regulator of podoplanin in tumor cells.
血小板反应蛋白-1在肿瘤中表达增加，其表达与肿瘤恶性程度相关。癌细胞上的血小板反应蛋白-1作为血小板聚集因子，与转移潜能相关。然而，血小板反应蛋白-1的调节因子仍有待确定。转化生长因子-β（TGF-β）调节许多生理过程，包括肿瘤发生。在此，我们发现TGF-β可诱导人纤维肉瘤HT1080细胞中血小板反应蛋白-1的表达，并增强HT1080细胞的血小板聚集能力。TGF-βⅠ型受体抑制剂（SB431542）和针对Smad4的短发夹RNA可抑制TGF-β诱导的血小板反应蛋白-1表达。这些结果表明，TGF-β是肿瘤细胞中血小板反应蛋白-1的生理调节因子。
