Abstract 1393: CD44 has dual functions to enhance the hyaluronan-induced chemokinesis in cancer cells as an associated molecule of hyaluronidase2-mediated HA catabolism and a hyaluronan receptor for RhoGTPase activation

Abstract

Major oncogenic signaling pathways are involved in the alteration of hyaluronan (HA) metabolism of cancer cells, such as Erb B, Wnt, TGF-β and p53 signalings. HA is a widely distributed extracellular matrix glycosaminoglycan and changes biological activities depending on its molecular sizes. Our recent study has shown that fragmented low molecular weight (LMW) HA (approximately 20 kDa) is an autocrine chemokinetic motility factor supported by the HA synthethase2-hyaluronidase2 / CD44 system on the plasma membrane of the cancer cells. In HeLaS3 cells, LMW-HA stimulation effectively enhanced cell spreading and random cell movement (chemokinesis) among different molecular sizes of HA (3, 23, 230, 940-kDa). Biochemically, LMW HA effectively provoked a RhoA activation, recurrent Cdc42 and Rac1 activation, and sustained phosphorylation of ERK1/2. Constrastly, 220 kDa HA did not enhance chemokinesis of HeLaS3 cells with similar activation profiles of Rac1 and ERK 1/2 except for the progressive decrease of Cdc42 and RhoA activation. The transfection of CD44 si-RNA to HeLaS3 cells abolished the enhanced chemokinesis with the remarkable decrease of Rho GTPase activation even in LMW HA stimulation. Accordingly, our study showed that CD44 has dual functions to enhance the HA-induced chemokinesis in cancer cells as an associated molecule of hyaluronidase2-mediated HA catabolism and a HA receptor for RhoGTPase activation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1393. doi:10.1158/1538-7445.AM2011-1393