Abstract A67: Defining signaling pathways governing metastatic potential in pancreas cancer
Pancreas cancer is an aggressively metastatic disease in which circulating tumor cells (CTC) often colonize distant organs long before diagnosis. Approximately 45% of patients present at diagnosis with metastatic disease, and this increases to 90% at the time of death. Even after surgical resection of the primary tumor, local and distant recurrence develops in approximately two thirds of cases. These sobering statistics highlight the need to define mechanisms and vulnerabilities of metastasis that can be targeted to improve patient outcomes. To better understand the process of pancreatic cancer metastasis, we study the Kras LSL-G12D/+ ; Trp53 LSL-R172H/+ ; Pdx1-Cre ( KPC ) model of autochthonous pancreas cancer. KPC mice spontaneously develop invasive and metastatic disease to numerous sites, including the liver and lungs, at rates similar to those seen in humans. Lineage tracing, performed by selectively expressing fluorescent reporters in pancreatic cells of KPC mice, has revealed a rare population of CTC that may be precursors to these metastatic foci. Building on this model, we show that alteration of TGFβ pathway components significantly affects the metastatic potential of autochthonous tumors, and that the timing and balance of signaling is critical in the metastatic process. These differences in metastatic potential are reflected in the numbers and functional properties of the respective CTC. Our distinct models with drastically different metastatic potentials provide clues to understanding the signaling mechanisms driving metastasis in pancreas cancer. Citation Format: Martin C. Whittle, Markus Carlson, Sunil R. Hingorani. Defining signaling pathways governing metastatic potential in pancreas cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A67.