Cancer-associated fibroblasts and epithelial-mesenchymal transition in metastatic oral tongue squamous cell carcinoma

Marilena Vered*, Dan Dayan, Ran Yahalom, Alex Dobriyan, Iris Barshack, Ibrahim O. Bello, Saara Kantola, Tuula Salo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


We examined cancer-associated fibroblasts (CAFs) and a panel of immunohistochemical markers of epithelial-mesenchymal transition (EMT) in 19 pair-matched oral tongue squamous cell carcinoma (SCC) and metastatic tumors to regional lymph nodes (RLNs). α-Smooth muscle actin (α-SMA) was studied to identify CAFs. EMT was studied with syndecan-1, Cadherin-11, fibroblast-specific protein (FSP)-1, secreted protein acidic and rich in cysteine (SPARC) and Twist. Triple immunostaining in RLNs was used to highlight the carcinoma cells (E-cadherin and Ki-67) and their relationship to the CAFs (α-SMA). We found that metastatic RLNs hosted CAFs similarly as in pair-matched primary tumors. Expression of EMT markers is common in both primary and metastatic tumors. We demonstrate that metastatic carcinoma cells (Ki-67 positive) downregulate E-cadherin expression at the periphery of cancer islands, where they are in direct contact with CAFs. The supporting connective tissue microenvironment also commonly expresses syndecan-1, Cadherin-11, FSP-1, and SPARC. In conclusion, CAFs are common to both primary and metastatic SCC. We hypothesize that CAFs not only promote tumor invasion but also facilitate metastases, either by cometastasizing and/or being recruited to lymph nodes. Evidence of EMT is common within primary tumors and metastatic SCC and may be further modulated by CAFs.

Original languageEnglish
Pages (from-to)1356-1362
Number of pages7
JournalInternational Journal of Cancer
Issue number6
StatePublished - 1 Sep 2010


  • Cancer-associated fibroblasts
  • Epithelial-mesenchymal transition
  • Oral tongue cancer
  • Regional lymph node metastasis
  • Tumor microenvironment


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