Abstract:
OBJECTIVES:Cancer-associated fibroblasts (CAFs) play an important role in tumor progression and are associated with a poor prognosis. Tumor necrosis factor α (TNFα) has been involved in growth and metastasis associated with epithelial-mesenchymal transition (EMT) in many types of cancers. However, the relationship among the TNFα, activation of CAFs and their tumor-promoting effects on tongue squamous cell carcinoma (TSCC) remain obscure. MATERIALS AND METHODS:A series of matched primary CAFs and normal fibroblasts (NFs) pairs were cultured, and additionally two TSCC cell lines SCC9 and CAL27, were treated with TNFα or CAFs derived stromal cell-derived factor-1 (SDF1) respectively to study invasion and EMT in vitro. In addition, NFs were treated with TNFα to detect the expression of myofibroblast markers, invasion, induced collagen gel contraction and enhanced cancer metastasis. Finally, invasion and angiogenesis of human vein endothelial cells (HUVECs) treated with TNFα and CAFs derived SDF1 was measured. RESULTS:TNFα and CAFs-derived SDF1 induced TSCC cells metastasis and EMT separately. TNFα facilitated the transformation of NFs to CAFs-like fibroblasts, which was accompanied by acquisition of similar myofibroblast markers expression and malignant function to CAFs. Furthermore, TNFα and CAFs derived SDF1 also promoted invasion and angiogenesis of HUVECs. CONCLUSION:These results suggest that TNFα may not only directly but also indirectly enhance cancer metastasis, EMT and angiogenesis formation in tongue cancer through myofibroblast differentiation via SDF1 secretion.
journal_name
Oral Oncoljournal_title
Oral oncologyauthors
Zhou B,Zhuang XM,Wang YY,Lin ZY,Zhang DM,Fan S,Li JS,Chen WLdoi
10.1016/j.oraloncology.2015.08.017subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1095-102issue
12eissn
1368-8375issn
1879-0593pii
S1368-8375(15)00320-6journal_volume
51pub_type
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