期刊
INTERNATIONAL JOURNAL OF CANCER
卷 127, 期 6, 页码 1356-1362出版社
WILEY
DOI: 10.1002/ijc.25358
关键词
oral tongue cancer; regional lymph node metastasis; cancer-associated fibroblasts; epithelial-mesenchymal transition; tumor microenvironment
类别
资金
- Dave and Sarah Babish Fund
- Academy of Finland
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). alpha-Smooth muscle actin (alpha-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 (alpha-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.
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