LAUSR

Breast cancer commonly gives rise to lymph node metastases, and it has been suggested that tumor cell migration is facilitated by the generation of new lymphatic vessels, or lymphangiogenesis. Lymphatic endothelial cell hyaluronic acid receptor 1 (LYVE-1) is a hyaluronic acid (HA) receptor commonly used as a lymphatic vessel endothelial marker. LYVE-1 has been observed in a variety of breast cancer epithelial cells, and its lymphangiogenic function remains unclear. LYVE-1 has been casually linked to the vascular endothelial growth factors VEGF-C and VEGF-D, which are well appreciated for their roles in lymphangiogenic responses. Therefore, we hypothesize that LYVE-1 may impact lymphangiogensis via a VEGF-C/VEGF-D mediated pathway. We utilized LYVE-1-targeted RNAi in MDA-231 cells followed by HA stimulation and measured production and secretion of both VEGF-C and VEGF-D by western blot and ELISA, respectively. Surprisingly, LYVE-1 knockdown resulted in elevated levels of basal VEGF-C secretion, while LYVE-1 knockdown followed by HA stimulation decreased secreted levels of VEGF-C, with no observed changes in intracellular levels when compared to their controls. Conversely, LYVE-1 knockdown displayed no significant changes in basal VEGF-D levels, although, secreted VEGF-D levels were elevated following HA stimulation. Collectively, our preliminary findings suggest that LYVE-1 modulates VEGF-C/D secretion, potentially defining a novel function for LYVE-1 in MDA-231 triple negative breast cancer epithelial cells. Citation Format: Sara Caceres, Andrew C. Little, Joel A. Yates, Rabia A. Gilani, Sofia D. Merajver. Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) modulates VEGF-C and VEGF-D secretion in the triple negative breast cancer cell line MDA-MB-231 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2044.