Angiopoietin like-4 (ANGPTL4), a 45 kDa protein is a key regulator of angiogenesis. In this study, we plan to look at the relationship between the expression and lymphangiogenic activity of ANGPTL4 in Head and Neck Squamous Cell Carcinoma (HNSCC). We evaluated the cellular expression of ANGPTL4 in a panel of HNSCC cell lines. We found that the HNSCC cells (HN4, HN6, HN12, and HN13) express higher levels of ANGPTL4 protein in comparison to Normal Oral Keratinocyte-Spontaneously Immortalized (NOK-SI) and Leukoplakia (Leuk-1) cell lines. Upon evaluating the conditioned media, we found that HNSCC cells also secrete higher levels of ANGPTL4 as compared to NOK-SI and Leuk-1 cells. Hypoxia, a key regulator of lymphangiogenesis has been shown to upregulate ANGPTL4 expression through stabilization of Hypoxia Inducible Factor (HIF)-1 alpha. We did not observe major differences in cellular expression of ANGPTL4 when cells were placed under hypoxic conditions. Interestingly, an increase in secretion of the full-length ANGPTL4 occurred under hypoxic conditions in all of the cell lines. We then investigated the role of Epidermal Growth Factor Receptor (EGFR) signaling induced lymphangiogenesis through ANGPTL4. We found that ANGPTL4 expression was reduced in HN6 and HN13 cell lines upon use of EGFR inhibitors. We hypothesized that ANGPTL4 secreted by oral cancer cells promotes lymphangiogenesis through promotion of cellular survival, proliferation, and migration of lymphatic endothelial cells (LECs). Preliminary data showed that the addition of recombinant full length-ANGPTL4 and C-terminal ANGPTL4 induced migration of LECs. In summary, our data shows that ANGPTL4 expression and secretion is elevated in HNSCC. ANGPTL4 promotes lymphangiogenesis by promoting migration of LECs. This makes ANGPTL4 a potential diagnostic marker and a viable target in treatment of HNSCC.

ANGPTL4 promotes lymphangiogenesis in head and neck squamous cell carcinoma

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.