Abstract 5232: Tumor-adipose microenvironment drives progression in advanced oral squamous cell carcinoma

Abstract Advanced oral squamous cell carcinoma (OSCC) is an aggressive cancer with a recurrence rate of 40-60%, and lymph node metastasis (LNM) occurs in 50% of cases, serving as a critical prognostic factor. Recent evidence suggests that fatty acid oxidation (FAO) enhances cancer cell survival, invasiveness, and therapeutic resistance. OSCC's histological proximity to dense adipose tissue provides a unique opportunity for cancer cells to acquire energy from the adipose environment, underscoring the importance of elucidating the tumor-adipose interactions in OSCC progression and metastasis. In this study, we investigated the impact of the tumor-adipose microenvironment on OSCC progression, focusing on interactions between adipocytes and cancer cells. Human adipose-derived stem cells (ADSCs) were differentiated into adipocytes and co-cultured with the OSCC cell line YD10B for three weeks to induce cancer-associated adipocytes (CAAs). Co-cultured adipocytes exhibited fibroblast-like phenotypic changes, reduced expression of adipogenic differentiation markers, and increased free fatty acid release. Inflammatory cytokines (e.g., IL-6) and tumor-promoting proteins (e.g., IGFBP-2) were upregulated. YD10B cells exposed to co-cultured adipocytes showed enhanced proliferation, invasion, and epithelial-mesenchymal transition (EMT) signaling. Adipocytes and cancer cells both showed increased expression of matrix metalloproteinases (MMP-2 and MMP-9), indicating mutual reinforcement of tumor aggressiveness. Collectively, these findings indicate that adipocytes, through their interaction with OSCC cells, undergo changes to acquire a CAA-like phenotype , which support tumor progression by providing fatty acids as an energy source and promoting aggressive phenotypes, including proliferation, invasion, and LNM. Targeting tumor-adipocyte interactions could offer novel therapeutic strategies to mitigate OSCC progression and improve outcomes. Citation Format: Gyeongmin Kang, Mi Rim Lee, Sumin Kang, Yu-Sun Lee, Hye Won Shon, Jiyoung Lee, Sung Weon Choi, Sun Il Choi, Yun-Hee Kim. Tumor-adipose microenvironment drives progression in advanced oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5232.