Abstract 584: Context-dependent roles of sFRP1 in melanoma.

Abstract Elevated levels of secreted Frizzled-Related Protein 1 (sFRP1) in melanoma patient datasets correlate with reduced overall and distant metastasis-free survival, suggesting a clinically significant role in disease progression. To explore the mechanisms underlying this association, we compared melanoma cell lines with differing basal sFRP1 levels and assessed proliferation, migration, and invasion following sFRP1 overexpression or knockdown. Proliferation was measured with standard assays, while migration and invasion were quantified using scratch and Boyden chamber assays. Across cell lines, sFRP1 produced divergent phenotypic outcomes, indicating that its activity is highly context-specific. Preliminary mechanistic analyses suggest that sFRP1 does not act through a single canonical pathway; instead, it appears to influence components of the tumor microenvironment, including markers linked to immune-regulatory pathways. These context-dependent changes highlight a broader role for sFRP1 in shaping interactions between melanoma cells and their surrounding microenvironment. Overall, these findings support a model in which sFRP1 modulates melanoma progression through multifactorial, microenvironment-dependent mechanisms rather than exerting uniformly oncogenic or suppressive effects. The impact of sFRP1 on melanoma appears shaped by intrinsic features of individual tumors. Ongoing studies aim to define the mechanisms, extracellular pathways, and tumor contexts that determine sFRP1-driven phenotypes and their potential clinical relevance. Citation Format: Cierra Perron, Douglas Quilty, Farzaneh Afzali, Bianca Dauber, Tyler Cooper, Krista M. Vincent, Ivan Topisirovic, Lynne-Marie Postovit. Context-dependent roles of sFRP1 in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 584.