Abstract 3193: Expression analysis reveals candidate genes involved in highly invasive high-hyaluronan binding subpopulations of prostate cancer cell lines

Abstract

Abstract Tumour heterogeneity is one of the hallmarks of aggressive cancers, which can be detected by differential gene expression, DNA mutation patterns, and ligand binding profiles. Hyaluronan (HA) is an extracellular matrix polysaccharide whose elevated accumulation is associated with tumour recurrence in colon and breast carcinomas. Previously, we reported that triple-negative breast cancer cell lines exhibit heterogeneous binding of HA, with high and low binding subpopulations showing differences in proliferation and invasion. Here we assessed whether or not a similar binding heterogeneity detects prostate cancer cell subsets with differential invasive capability. Flow cytometry HA-binding profiles reveal heterogeneous binding of a fluorescent HA probe to the PC3M-LN4 prostate cancer cell line. Fluorescence-activated cell sorting (FACS) was used to isolate low and high hyaluronan binding subpopulations. Sorted cells were cultured and, after one week of growth, were analyzed for cell proliferation and invasion using alamar blue, transwell invasion and gelatin degradation assays. Results confirmed that HAhigh tumor cells displayed reduced growth but increased invasion and degradation relative to HAlow subpopulations. We then employed human gene 2.0 expression arrays to assess transcriptome changes between these two subpopulations. The expression of 7 genes was significantly elevated or lowered in HAhigh vs. HAlow cells, and these were linked to inflammation, angiogenesis, MMP9 regulation and metastasis. These results identify a novel form of heterogeneity common to both breast and prostate cancer cell lines and suggest that subpopulations binding high levels of HA can be used as indicators of aggressive tumors. Citation Format: Sean J. Leith, Ann F. Chambers, James B. McCarthy, Joseph L. Chin, Eva A. Turley. Expression analysis reveals candidate genes involved in highly invasive high-hyaluronan binding subpopulations of prostate cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3193. doi:10.1158/1538-7445.AM2015-3193