Moreover, HA stimulates EC tube formation via CD44 and CD168/TGFβ Receptor I signaling, which promote plasminogen activator-inhibitor-1 (PAI-1) expression and subsequently ICAM-1, VCAM-1, and MMP-2 expression, thereby promoting tumor angiogenesis (93, 143, 144). This evidence concerns the gene SERPINE1 and neoplasm.