Targeting galectin-1-induced angiogenesis mitigates the severity of endometriosis.

BASTON JI; BARAÑAO RI; RICCI AG; BILOTAS MA; OLIVARES CN; SINGLA JA; GONSALEZ AM; STUPIRSKI JC; CROCI DO; RABINOVICH GA; MERESSMAN GA

JOURNAL OF PATHOLOGY

JOHN WILEY & SONS LTD

Lugar: LOndres; Año: 2014 vol. 2014 p. 329 - 337

0022-3417

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that causes severe pelvicpain and infertility in women of reproductive age. Although not completely understood, the pathophysiology of thedisease involves chronic dysregulation of inflammatory and vascular signalling. In the quest for novel therapeutictargets, we investigated the involvement of galectin-1 (Gal-1), an endogenous glycan-binding protein endowedwith both immunosuppressive and pro-angiogenic activities, in the pathophysiology of endometriotic lesions. Herewe show that Gal-1 is selectively expressed in stromal and endothelial cells of human endometriotic lesions. Usingan experimental endometriosis model induced in wild-type and Gal-1-deficient (Lgals1−/−) mice, we showed thatthis lectin orchestrates the formation of vascular networks in endometriotic lesionsin vivo, facilitating their ectopicgrowth independently of vascular endothelial growth factor (VEGF) and the keratinocyte-derived CXC-motif(CXC-KC) chemokine. Targeting Gal-1 using a specific neutralizing mAb reduced the size and vascularized areaof endometriotic lesions within the peritoneal compartment. These results underline the essential role of Gal-1during endometriosis and validate this lectin as a possible target for the treatment of disease.