“Molecular determinants of desmoid tumor development and progression.” Year 1 of 3

These investigators will be studying three molecular factors believed to be important in desmoid tumors: beta catenin, TCF-3 (a transcription factor) and ER-beta (an estrogen receptor). They are using a three-pronged approach. Aim 1 is the establishment of multiple desmoid tumor cell lines. Aim 2 is the examination of the role of beta catenin, TCF-3 and ERbeta interactions in desmoid proliferation using the cell lines developed in Aim 1. Aim 3 is the identification of desmoid tumor related molecular markers using oligoarrays and tissue microarrays.

A small portion of stem cells in a given tissue give rise to all of the cells that make up that tissue. These cells help regenerate and maintain the tissue over its lifespan. These stem cells have been identified in a variety of tumor types and are called tumor initiating cells (TIC). These investigators will be testing the hypothesis that desmoid tumors contain a subpopulation of TIC and that desmoid tumors are derived from mesenchymal stem cells (MSC) that have a mutation leading to elevated levels of beta catenin, a protein thought to be instrumental in the development of familial adenomatous polyposis along with a mutation in the APC gene. In familial cases, desmoid tumors are associated with an APC mutation. Preliminary data suggest that desmoid tumors may be derived from MSC’s in which beta catenin signaling is misregulated. Dr. Alman and his team currently have 22 desmoid tumor cell lines with which to work. They will be (1) attempting to identify cell lines of TICs in desmoid tumors using established surface markers, and (2) using mice to determine if the tumors arise from misregulated MSC’s. Their goal is to ultimately develop a novel strategy of targeting desmoid tumor initiating cells.