Abstract B41: HGFL-Ron signaling enhances breast cancer stem cell populations

The Ron receptor tyrosine kinase is overexpressed in a high fraction of human breast cancers (BCs). Ron and its ligand, the Hepatocyte Growth Factor-Like protein (HGFL), play important roles during BC initiation, progression, and therapeutic resistance, with overexpression of this signaling cascade associated with increased BC metastasis and poor prognosis in humans. Reports demonstrate that a small subpopulation of cancer cells, called the breast cancer stem cells (BCSCs), are essential for the development and maintenance of BC, leading to tumor formation and recurrence. Despite the role of HGFL-Ron signaling as a key regulator of BC, nothing is known about this signaling pathway in BCSC populations. To investigate the function of HGFL-Ron signaling in BCSCs, the expression levels of Ron and HGFL were analyzed in BCSCs. mRNA analyses show increased levels of Ron and HGFL in BCSC-enriched Mammospheres (MSs) compared to parental BC epithelial cells. Next, the association between Ron signaling and the BCSC population was examined. Aldefluor assays of several Ron replete and depleted human and murine BC epithelial cell lines show that Ron overexpression increases the BCSC population. In vivo, flow cytometry analyses of breast tumors for BCSC markers show that Ron signaling is associated with increases in the BCSC population. MS formation assays using several Ron replete and depleted human and murine BC cell lines also demonstrate that cells expressing high levels of Ron have inc...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research