Osteopontin Splicing Isoforms Contribute to Endometriotic Proliferation, Migration, and Epithelial-Mesenchymal Transition in Endometrial Epithelial Cells

Osteopontin (OPN) isoforms, including OPNb and OPNc, promote malignancy and may contribute to the pathogenesis of endometriosis, a benign disorder with multiple characteristics resembling malignant tumors. In our experiments, OPNb and OPNc were significantly overexpressed in both endometriosis and adenomyosis compared to the normal endometrium. Upregulation of CD44v and the epithelial-mesenchymal transition (EMT) process was also present in endometriotic lesions. Overexpression of OPNb and OPNc splicing variants in endometriotic cells evoked morphological changes, actin remodeling, cell proliferation, cell migration, and EMT through binding OPN ligand receptors CD44 and alpha v beta 3, subsequently activating the PI3K and NF-kappa B pathways. We elucidated the causal role of OPN splice variants in regulating endometriotic cell growth, which may promote the development of OPN-targeted therapies for patients suffering from endometriotic disorders.

Automated summary

OPNb and OPNc are overexpressed in endometriosis and adenomyosis, and CD44v and the epithelial-mesenchymal transition (EMT) process are also upregulated. Overexpression of OPNb and OPNc splice variants leads to morphological changes, actin remodeling, cell proliferation, cell migration, and EMT through binding with CD44 and alpha v beta 3, subsequently activating the PI3K and NF-kappa B pathways.