Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity

Abstract

Tumor angiogenesis is a key event in cancer progression. Here, we report that tumors can stimulate tumor angiogenesis by secretion of galectin-1. Tumor growth and tumor angiogenesis of different tumor models are hampered in galectin-1-null (gal-1 −/− ) mice. However, tumor angiogenesis is less affected when tumor cells express and secrete high levels of galectin-1. Furthermore, tumor endothelial cells in gal-1 −/− mice take up galectin-1 that is secreted by tumor cells. Uptake of galectin-1 by cultured endothelial cells specifically promotes H-Ras signaling to the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) kinase (Mek)/Erk cascade and stimulates endothelial cell proliferation and migration. Moreover, the activation can be blocked by galectin-1 inhibition as evidenced by hampered membrane translocation of H-Ras.GTP and impaired Raf/Mek/Erk phosphorylation after treatment with the galectin-1-targeting angiogenesis inhibitor anginex. Altogether, these data identify galectin-1 as a proangiogenic factor. These findings have direct implications for current efforts on galectin-1-targeted cancer therapies. Cancer Res; 70(15); 6216-24. ©2010 AACR.

Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma

“…Several tumor characteristics have been identified to be vasculature of several human malignant tumors. 36 More specifically, the uptake of galectin-1 by cultured endothelial cells promotes H-Ras signaling and stimulates endothelial cell proliferation and migration. 36 Conversely, knockdown of galectin-1 expression in endothelial cells was shown to inhibit proliferation and migration, and galectin-1-null mice displayed hampered tumor growth due to decreased angiogenic activity.…”

“…36 More specifically, the uptake of galectin-1 by cultured endothelial cells promotes H-Ras signaling and stimulates endothelial cell proliferation and migration. 36 Conversely, knockdown of galectin-1 expression in endothelial cells was shown to inhibit proliferation and migration, and galectin-1-null mice displayed hampered tumor growth due to decreased angiogenic activity. 37 These results suggest that the active role galectin-1 plays in the proliferation and migration of tumors is via angiogenesis.…”

Presence of galectin-1 in the epidermal and dermal thickening of keloid tissues

“…Interestingly, abnormal vascularization has been associated not only with pronounced proliferation of endothelial cells [60] and hypoxia [11,61], but also with an elevated Gal-1 expression [62,63]. In fact, studies have shown that Gal-1 can induce endothelial cell proliferation [64,65] and that Gal-1 expression can be regulated by hypoxia [66,67]. Also of significance, some studies have provided evidence that local hypoxia not only promotes keratinocyte motility and migration during wound healing [68] but also stimulates the deposition of collagen by fibroblasts in wounds and keloids [69][70][71] and abnormal vascularization in keloids [11].…”

Glycans and Galectins: Sweet New Approaches in Pancreatic Cancer Diagnosis and Treatment

“…Moreover, Gal-1 modulates the expression of BEX2 and several hypoxia related genes involved in angiogenesis. Paracrine mechanisms involving the uptake by endothelial cells of Gal-1 secreted from tumoral cells have been linked to endothelial cell activation and tumor angiogenesis stimulation, through Ras and Erk1/2 activation (Thijssen et al, 2010).…”