Abstract 1566: Influence of age on fibroblast derived extracellular vesicles and their role in melanoma progression

Abstract

Abstract Age is an important prognostic factor in cutaneous melanoma, which commonly arises in the elderly. Melanoma progression is the concerted outcome of cellular and molecular changes that occur not just within the tumor cells but also within the milieu of the stromal cells (fibroblasts, immune cells, adipocytes), collectively referred to as the tumor microenvironment (TME). Moreover, TME-secreted growth factors, cytokines, and extracellular matrix (ECM) are vital to tumor progression and therapy resistance. Aging causes remodeling of the TME that becomes conducive to melanoma progression. In addition, extracellular vesicles (EVs) have been shown to transport lipids, mRNAs and functional proteins between different cells in vitro and across tissues in vivo. EVs have also been shown to play an important role in tumor progression in different cancer types, and aging can change their composition as well as their cargo. We performed proteomics on EVs released by young and aged dermal fibroblasts, the predominant stromal cell population of melanoma TME, to investigate how aging of the cells changes the EVs released by them. Moreover, we performed functional assays to investigate what influence this will have on the tumor progression. Our study shows that EVs secreted by dermal fibroblasts change in their composition as well as their cargo adding another dimension to age-associated increase in melanoma progression, and therapy resistance. Citation Format: Laura Hueser, Yash Chhabra, Olesia Gololobova, Mitchell Fane, Kenneth Witwer, Ashani Weeraratna. Influence of age on fibroblast derived extracellular vesicles and their role in melanoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1566.