Abstract B05: Mesenchymal-driven hedgehog signaling drives tumor cell growth and is a potential new target for triple-negative breast cancer

Triple negative breast cancer (TNBC) is a clinical therapeutic challenge due to the lack of receptors for estrogen, progesterone, and human epidermal growth factor receptor 2 which limits treatment options to chemotherapy and radiation. With current standard therapy less than 30% will survive the 5-year remission rate, especially Hispanic and African-American women where TNBC is more frequent and has the lowest (<14%) 5-year survival rates. Recent studies indicate that Hedgehog (Hh) signaling is active and correlates with reduced survival rates in TNBC patients. However, the role of the Hh signaling in the breast tumor microenvironment is not well understood. A main cellular mediator of Hh signaling is the adjacent mesenchyme which promotes tumor growth via a paracrine interaction, but which is also highly heterogeneous. As mesenchymal sub-types have been associated to specific pharmacological therapies, understanding of the mechanisms in mesenchymal-driven tumors is necessary for combinatorial pharmacological treatments that can increase survival rates and eliminate tumor relapse in patients. We developed a tumor-mesenchymal in vitro model to evaluate the role of mesenchymal cell sub-types from different sources in the proliferative potential and stem cell markers of breast cancer cells using a custom designed multiwell array. Cells were culture in adjacent compartments and active Hh signaling was confirmed by up-regulation of canonical Hh target genes Gli1, Patch1 and SM...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways: Hedgehog: Poster Presentations - Proffered Abstracts Source Type: research