FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis

Wang，Yujie1; Sun，Qi2; Ye，Ying3; Sun，Xiaoting2,4; Xie，Sisi2; Zhan，Yuhang2; Song，Jian1; Fan，Xiaoqin1; Zhang，Bin1; Yang，Ming5; Lv，Lei6; Hosaka，Kayoko4; Yang，Yunlong1,2; Nie，Guohui1,7

2022-05-23

10.1172/jci.insight.157874

JCI Insight   影响因子和分区

2379-3708

Molecular signaling in the tumor microenvironment (TME) is complex, and crosstalk among various cell compartments in supporting metastasis remains 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 that an elevation of FGF-2 signaling in samples from patients with nasopharyngeal carcinoma (NPC) and xenograft mouse models promoted 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 toward 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 liposome 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 TAMmediated metastasis. We provide mechanistic insight into an FGF-2/FGFR1/pericyte/CXCL14/TAM stromal communication axis in NPC and propose an effective antimetastasis therapy concept by targeting a pericyte-derived inflammation for NPC or FGF-2hi tumors.

SCI

英语

其他

National Natural Science Foundation of China[81773059,82192865,81970875] ; National Program on Key Research[2021YFA0804703] ; Program for Professor of Special Appointment in Shanghai[TP2018007] ; National Key Research and Development Project["2020YFC1316900","2020YFC1316901","2020YFC2005200"] ; Natural Science Foundation of Guangdong Province[2019A1515011495] ; Shenzhen Science and Technology Innovation Committee["ZDSYS201707281114196","KCXFZ20201221173413038","JCYJ20180508152528735","JCYJ20170306091657539"] ; Sanming Project of Medicine in Shenzhen[SZSM201612031]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000802222200001

AMER SOC CLINICAL INVESTIGATION INC

2-s2.0-85130717284

Scopus

1.Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research,Department of Otolaryngology,Shenzhen Institute of Translational Medicine,The First Affiliated Hospital of Shenzhen University,Shenzhen Second People's Hospital,Shenzhen,Guangdong,China
2.Department of Cellular and Genetic Medicine,School of Basic Medical Sciences,Fudan University,Shanghai,China
3.Department of Oral Implantology,School and Hospital of Stomatology,Tongji University,Shanghai Engineering Research Center of Tooth Restoration and Regeneration,Shanghai,China
4.Department of Microbiology Tumor and Cell Biology,Karolinska Institutet,Stockholm,Sweden
5.Department of Otolaryngology,Shenzhen People's Hospital,the Second Clinical Medical College,Jinan University,the First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,Guangdong,China
6.Ministry of Education Key Laboratory of Metabolism and Molecular Medicine,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Fudan University,Shanghai,China
7.State Key Laboratory of Chemical Oncogenomics,Guangdong Provincial Key Laboratory of Chemical Genomics,Peking University,Shenzhen Graduate School,Shenzhen,Guangdong,China

Wang，Yujie,Sun，Qi,Ye，Ying,et al. FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis[J]. JCI Insight,2022,7(10).

Wang，Yujie.,Sun，Qi.,Ye，Ying.,Sun，Xiaoting.,Xie，Sisi.,...&Nie，Guohui.(2022).FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis.JCI Insight,7(10).

Wang，Yujie,et al."FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis".JCI Insight 7.10(2022).