title: A role for cancer-associated fibroblasts in inducing the epithelial-to-mesenchymal transition in human tongue squamous cell carcinoma.
abstract: OBJECTIVE
  Lymph node metastasis is a prominent clinical feature of tongue squamous cell carcinoma (TSCC) and is associated with a higher mortality rate. Carcinoma-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play an important role in tumor progression, and are associated with a poor prognosis. The aim of this study was to examine the role of CAFs in promoting the invasion of TSCC through the epithelial-to-mesenchymal transition (EMT).
  
  
  METHODS
  A series of matched CAF and normal fibroblast (NF) pairs were assessed for cell morphology and for the expression of alpha smooth muscle actin (α-SMA), stromal cell-derived factor-1 (SDF1), fibroblast-activating protein (FAP), vimentin, and cytokeratin (CK) markers. Transwell assays, Western blot analysis, reverse transcription-PCR, and immunofluorescence staining were used to assess the role of CAFs, as compared to that of NFs, in promoting proliferation, migration, invasion, and EMT in TSCC.
  
  
  RESULTS
  Both CAF and NF primary cultures expressed vimentin but not CK. CAFs showed significantly higher α-SMA protein levels, SDF1 secretion, and mRNA levels of α-SMA, SDF1, and FAP. We also found that co-culture with CAFs enhanced the proliferation and invasion of SCC9 cells. Moreover, co-culture with CAFs induced upregulation of the EMT markers fibronectin and vimentin, downregulation of E-cadherin, and enhanced invasion in SCC9 cells.
  
  
  CONCLUSIONS
  These results suggest that CAFs induce EMT marker expression and functional changes in TSCCs.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Chen
authors.forename: You-Yuan
authors.initials: YY
authors.lastname: Wang
authors.forename: Zhao-Yu
authors.initials: ZY
authors.lastname: Lin
authors.forename: Da-Ming
authors.initials: DM
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Fan
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Li
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000032:analysis; D018920:Coculture Techniques; D010450:Endopeptidases; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000473:pathology* / Q000502:physiology; D005353:Fibronectins / Q000032:analysis; D018093:Gelatinases / Q000032:analysis; D006801:Humans; D007633:Keratins / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012697:Serine Endopeptidases / Q000032:analysis; D014062:Tongue Neoplasms / Q000473:pathology*; D059016:Tumor Microenvironment / Q000502:physiology; D014746:Vimentin / Q000032:analysis; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000199:Actins; D000951:Antigens, Neoplasm; D015820:Cadherins; D054377:Chemokine CXCL12; D010450:Endopeptidases; D005353:Fibronectins; D018093:Gelatinases; D007633:Keratins; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D014746:Vimentin; D000099167:Fibroblast Activation Protein Alpha; C541116:ACTA2 protein, human
keywords: cancer-associated fibroblasts; epithelial-mesenchymal transition; tongue squamous cancer cells; tumor microenvironment