Abstract 5304: RNA sequencing of circulating tumor cells implicates WNT signaling in pancreatic cancer metastasis

Abstract

Abstract Circulating tumor cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While isolation and molecular analysis of these cells is technically challenging, they may identify cellular pathways that contribute to the blood-borne dissemination of cancer cells. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to digital gene expression (DGE) analysis using single molecule RNA sequencing. We identified Wnt2 as enriched in both CTCs and metastatic ascites cells, compared with primary tumors. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-β signaling. DGE analysis of human pancreatic CTCs reveals significant enrichment for non-canonical Wnt signaling in 5 of 11 cases, with Wnt2 RNA detectable by in situ hybridization in a subset of CTCs. Identifying CTC-enriched transcripts such as Wnt2 may point to pathways that enhance haematogenous metastasis, thus providing novel therapeutic targets to prevent the distal spread of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5304. doi:1538-7445.AM2012-5304