title: c-Met identifies a population of matrix metalloproteinase 9-producing monocytes in peritumoural stroma of hepatocellular carcinoma.
abstract: Macrophages (Mϕ) are prominent components of solid tumours and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumours could alter the normal developmental process of Mϕ to trigger transient activation of monocytes in the peritumoural stroma of human hepatocellular carcinoma (HCC). In the present study, we showed that a fraction of monocytes in the peritumoural stroma, but not in HCC cancer nests, expressed surface c-Met molecules. Monocytes exposed to tumours strongly expressed c-Met proteins with kinetics similar to their activation status, and significant correlations were found between c-Met levels and HLA-DR expression on tumour-infiltrating monocytes. NF-κB-mediated autocrine TNF-α stimulated the expression of c-Met on activated monocytes, and by interacting with its ligand hepatocyte growth factor (HGF), c-Met increased the motility and matrix metalloproteinase (MMP) 9-producing capacity of tumour-associated monocytes. The intensity of c-Met expression on tumour-infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC. Therefore, the expression of c-Met on activated monocytes/Mϕ may represent a novel mechanism by which a tumour actively and precisely regulates the distribution and functions of these cells to facilitate disease progression.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.|State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Xie
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Li
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.|State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement; D018920:Coculture Techniques; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D056945:Hep G2 Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008819:Mice, Nude; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C066855:HGF protein, human; D006684:HLA-DR Antigens; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: c-Met; hepatocellular carcinoma (HCC); matrix metalloproteinase (MMP) 9; monocyte