Abstract 218: R-Spondin (RSPO) signaling drives the growth of multiple human tumor types

The R-spondin-LGR signaling axis is a recently appreciated pathway that promotes beta-catenin signaling in normal stem cell populations. Beta-catenin signaling had long been considered synonymous with Wnt signaling. We conducted a reporter-based screen for secreted beta-catenin signaling activities produced by a panel of human tumors. This exercise and further molecular characterization efforts discovered RSPO activity produced by numerous human tumors of multiple tumor types including ovarian, pancreatic, colon, breast and non-small cell lung cancer. Specific antibody antagonists of RSPO family members were developed. In minimally passaged human tumor xenograft models, anti-RSPO treatment markedly inhibited tumor growth in several tumor types. Moreover, RPSO blockade promoted tumor differentiation and reduced the frequency of tumor initiating cells. These data highlight the potential for therapeutic intervention with this newly appreciated signaling axis. Citation Format: Austin Gurney, Cecile Chartier, Fumiko Axelrod, Jennifer Cain, Wan-Ching Yen, Christopher Murriel, Janak Raval, Marcus Fischer, Jalpa Shah, May Ji, Christopher Bond, Ann Kapoun, John Lewicki, Timothy Hoey. R-Spondin (RSPO) signaling drives the growth of multiple human tumor types. [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 218. doi:10.1158/1538-7445.AM2013-218