Abstract C033: Investigating the differential roles of HMGA2 isoforms in the bone microenvironment

Abstract

Abstract Prostate cancer (PCa) is the second leading cause of cancer related deaths in American men. Compared to Caucasian men, African American males have a higher bone density, as well as mortality rate due to bone metastasis. Recent studies have shown that High Mobility Group A2 (HMGA2), a non-histone chromatin binding protein, plays a critical role in promoting metastasis. HMGA2 full-length/wild-type and truncated (without the 3’UTR) isoforms have been shown to be overexpressed in several cancers, however their distinct roles in metastasis have not been reported. Our laboratory focuses on tumor-micronenvironmental interactions. We have previously published that PCa cells degrades hydroxyapatite, the major inorganic component of bone, to release calcium which promotes paracrine cell proliferation and migration, and this signaling increases with increased bone density. We hypothesize that HMGA2 isoforms may play differential roles at the bone metastatic site and effect paracrine cell proliferation and migration. LNCaP PCa cell line stably overexpressing either full length or truncated HMGA2 was co-cultured with low (100 mg) or high (200 mg) hydroxyapatite or human bone matrix powder, for 6 days followed by collection of conditioned media (CM). CM was co-cultured with parental LNCaP cells for various time points followed by analysis of several signaling pathways using western blot analysis, as well as analysis of paracrine cell proliferation using MTS assay, and cell migration across collagen using boyden chamber. Results reveal that co-culture of LNCaP cells expressing WT and TR HMGA2 with bone components has a paracrine effect on MAPK signaling. This was accompanied by a paracrine increase in cell migration but not cell proliferation with CM from truncated HMGA2-expressing cells co-cultured with bone, that can be abrogated by MAPK inhibition. Our study shows that wild-type and truncated isoforms of HMGA2 may differentially mediate PCa/hydroxyapatite bone interactions at the bone metastatic site, which may contribute to bone metastasis, particularly in African American men that have higher bone density. Acknowledgements: These studies were supported by NIH/NIGMS/RISE SR25GM060414 and NIH/NIMHD 2U54MD007590; 5U54MD013376-8281. Citation Format: Taaliah Campbell, Ohuod Hawsawi, Veronica Henderson, Valerie Odero-Marah. Investigating the differential roles of HMGA2 isoforms in the bone microenvironment [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C033.