title: Cancer-associated fibroblasts provide a suitable microenvironment for tumor development and progression in oral tongue squamous cancer.
abstract: BACKGROUND
  Oral tongue squamous cell carcinoma (OTSCC) is still associated with a poor prognosis due to local recurrence and metastasis. Cancer-associated fibroblasts (CAFs) play an important role in the complex processes of cancer stroma interaction and tumorigenesis. This study aims to determine the role of CAFs in the development and progression of OTSCC.
  
  
  METHODS
  Immunohistochemistry was performed to evaluate the frequency and distribution of CAFs in 178 paraffin specimens from patients with OTSCC. Immunofluorescence, a cell proliferation assay, flow cytometry, migration and invasion assays and western blot analysis were used to study the effects of CAFs and the corresponding conditioned medium (CM) on the proliferation and invasion of OTSCC cell lines.
  
  
  RESULTS
  Statistical analysis showed a strong correlation between the frequency and distribution of CAFs and the clinicopathological characteristics of patients with cN0 OTSCC, including pathological stage (P = 0.001), T classification (P = 0.001), and N classification (P = 0.009). Survival analysis demonstrated a negative correlation of the frequency and distribution of CAFs with the overall survival and disease-free survival of patients with cN0 tongue squamous cell cancer (P = 0.009, 0.002, respectively); Cox regression analysis showed that the presence of CAFs (relative risk: 2.113, CI 1.461-3.015, P = 0.023) is an independent prognostic factor. A functional study demonstrated that CAFs and CM from CAFs could promote the growth, proliferation, mobility, invasion and even Epithelial Mesenchymal Transition (EMT) of OTSCC cells compared with NFs and CM from NFs.
  
  
  CONCLUSIONS
  CAFs were an independent prognostic factor for patients with OTSCC. Compared with NFs, CAFs and their CM have the ability to promote the growth, proliferation, metastasis and even EMT of OTSCC cells.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. lihuan@sysucc.org.cn.|Department of Intensive Care, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. lihuan@sysucc.org.cn.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. zhangji1@sysucc.org.cn.|Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. zhangji1@sysucc.org.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. chenshuw@sysucc.org.cn.|Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. chenshuw@sysucc.org.cn.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. liull@sysucc.org.cn.|Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. liull@sysucc.org.cn.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. lilei@sysucc.org.cn.|Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. lilei@sysucc.org.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. gaofan@sysucc.org.cn.|Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. gaofan@sysucc.org.cn.
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. zhuangshm@sysucc.org.cn.
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Zhuang
authors.affiliation: The People's Hospital of Bao'an District Shenzhen, Shenzhen, People's Republic of China. wanglp@sysucc.org.cn.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. liyan@sysucc.org.cn.|Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. liyan@sysucc.org.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou, 510060, People's Republic of China. songming@sysucc.org.cn.|Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. songming@sysucc.org.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Song
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002452:Cell Count; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D048430:Cell Shape / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018450:Disease Progression; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D014062:Tongue Neoplasms / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned