CSF-1R promotes vasculogenic mimicry via epithelial-mesenchymal transition in nasopharyngeal carcinoma cells

Abstract

Objectives In nasopharyngeal carcinoma (NPC), the main factors for treatment failure are local recurrence and metastasis. Vasculogenic mimicry (VM), formation by invasive cancer cells mimicking the vasculogenic network, is strongly correlated with tumor therapy resistance and distant metastasis. CSF-1R was substantially expressed in NPC patients with a poor prognosis, according to an earlier study of ours. However, whether CSF-1R affects progression through vasculogenic mimicry deserves consideration. Methods By cultivating NPC cells that had CSF-1R overexpression in three-dimensional culture and labeling the NPC xenografts with CD34-PAS vasculogenic mimicry markers, the effect of CSF-1R on VM formation, migration, and invasion of NPC cells was evaluated. Finally, the underlying mechanisms were investigated by western blot. Results In vitro and in vivo, overexpressing CSF-1R in NPC cells causes the development of vessel-like structures. Meanwhile, NPC cells migrated and invaded more readily in the Transwell experiment when CSF-1R was highly expressed. Mechanistically, our research indicates that CSF-1R may control cell plasticity by activating the PI3K/AKT signaling pathway, promoting the formation of VM in these cells by facilitating the epithelial-mesenchymal transition. Conclusions CSF-1R in NPC progression by increasing VM production to increase nutrient supply to tumor cells and promote cancer cell invasion. Furthermore, these findings suggest that CSF-1R is a new promising therapeutic target aimed at treating VM in NPC.