LAUSR

Molecular signaling in the tumor microenvironment (TME) is complex, and crosstalks among various cell compartments in supporting metastasis remain poorly understood. In particular, the role of vascular pericytes, a critical cellular component in the TME, in cancer invasion and metastasis warrants further investigation. Here we report an elevation of FGF-2 signaling in both nasopharyngeal carcinoma (NPC) patient samples and xenograft mouse models promotes NPC metastasis. Mechanistically, tumor cell-derived FGF-2 strongly promoted pericyte proliferation and pericyte-specific expression of an orphan chemokine (C-X-C motif) ligand 14 (CXCL14) via FGFR1- AHR signaling. Gain and loss-of-function experiments validated that pericyte-derived CXCL14 promoted macrophage recruitment and polarization towards an M2-like phenotype. Genetic knockdown of FGF2 or genetic depletion of tumoral pericytes blocked CXCL14 expression and tumor-associated macrophage (TAM) infiltration. Pharmacological inhibition of TAMs by clodronate liposomes treatment resulted in a reduction of FGF-2-induced pulmonary metastasis. Together, these findings shed light on the inflammatory role of tumoral pericytes in promoting TAM-mediated metastasis. We provide mechanistic insight into an FGF-2-FGFR1-pericyte-CXCL14-TAM stromal communication axis in NPC and propose an effective anti-metastasis therapy concept by targeting a pericyte-derived inflammation for NPC or FGF-2-high tumors.