Abstract 371: PGI2 analog enhances endothelial-pericyte interactions and suppresses lung metastasis.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Endothelial cells (ECs) express IP (prostaglandin I2 (PGI2) specific receptor) and are playing important role in tumor angiogenesis. We have reported that the PGI2-IP system is necessary for vascular remodeling and angiogenesis. Additionally, we have reported that the knockdown of IP increases tumor metastasis in mouse models. Objectives: In this study, we examined whether the activated PGI2-IP signaling could enhance EC-PC interactions and suppress tumor metastasis. Materials & Methods: Mouse-derived Lewis lung carcinoma (LLC) cells were used for a mouse lung metastatic model, and were injected from the tail vein of mice (c57BL/6J). Beraprost sodium (BPS; PGI2 analog) was continuously administered for 3 weeks. Tumor metastasis to lung was assessed by using hematoxylin-eosin staining. The a-SMA and the NG2 as a pericyte marker and the endomucin as an endothelial cell marker were analyzed by immunofluorescence to evaluate angiogenesis in metastatic lung tumors. The structure of the tumor blood vessels was analyzed by scanning electron microscopy (SEM). Results: The size and number of lung metastatic nodules were significantly decreased in BPS group compared with in control group assessed by the mice lung metastatic model. Immunofluorescence analysis revealed that the number of vessel-associated a-SMA+ cells was significantly increased by BPS administration. Scanning electron microscopy revealed that pericytes covering the tumor blood vessels increased in BPS group. Conclusions: The present study demonstrated that BPS suppresses lung metastasis in our model. These results also suggested that the maturation of tumor blood vessels by pericytes may decrease tumor metastasis. Finally, we propose that BPS would be a novel therapeutic target in lung metastasis. Citation Format: Yoshinori Minami, Takaaki Sasaki, Satoshi Endo, Kiyoko Shibukawa, Yoshinobu Ohsaki. PGI2 analog enhances endothelial-pericyte interactions and suppresses lung metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 371. doi:10.1158/1538-7445.AM2013-371