Ying Liu, Ileana Murazzi, Ashley M Fuller, Hehai Pan, Valerie M Irizarry-Negron, Ann DeVine, Rohan Katti, Nicolas Skuli, Gabrielle E Ciotti, Koreana Pak, Michael A Pack, M Celeste Simon, Kristy Weber, Kumarasen Cooper, T S Karin Eisinger-Mathason
Intratumoral hypoxia correlates with metastasis and poor survival in sarcoma patients. Using an impedance sensing assay and a zebrafish intravital microinjection model, we demonstrated here that the hypoxia-inducible collagen-modifying enzyme lysyl hydroxylase PLOD2 and its substrate collagen type VI (COLVI) weaken the lung endothelial barrier and promote transendothelial migration. Mechanistically, hypoxia-induced PLOD2 in sarcoma cells modified COLVI, which was then secreted into the vasculature. Upon reaching the apical surface of lung endothelial cells, modified COLVI from tumor cells activated integrin β1 (ITGβ1)...
February 9, 2024: Cancer Research