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Journal of Dental Research, Vol. 87, No. 11, 1069-1074 (2008)
DOI: 10.1177/154405910808701111

Biological

Areca-treated Fibroblasts Enhance Tumorigenesis of Oral Epithelial Cells

H.-H. Lu1, C.-J. Liu1,2, T.-Y. Liu1,3, S.-Y. Kao1,4, S.-C. Lin1,* and K.-W. Chang1,4,*

1 Institute of Oral Biology, School of Dentistry, National Yang-Ming University, No. 155, Li-Nong St., Sec.2, Taipei, Taiwan 112;
2 Oral and Maxillofacial Surgery, Taipei Mackay Memorial Hospital, Taipei, Taiwan; and
3 Department of Medical Education and Research and
4 Department of Dentistry, Taipei Veterans General Hospital, Taipei, Taiwan

Correspondence: * corresponding authors, ckcw{at}ym.edu.tw and sclin{at}ym.edu.tw

Several hundred million Asians chew areca nut, which is strongly associated with oral carcinogenesis in people of this region. The impacts of areca nut extract on oral target cells are largely unclear. This study hypothesized an inductive role for areca-nut-exposed stromal cells in the progression of oral carcinomas in an at-risk population. Oral fibroblasts with chronic subtoxic areca nut extract treatment exhibited growth arrest and MMP-2 activation. The supernatant of arrested oral fibroblasts activated the AKT signaling pathway in oral carcinoma cells. The enhancement of proliferation, migration, and anchorage-independent growth of oral carcinoma cells elicited by such supernatant could be abrogated by blockers against MMP-2 or AKT. Subcutaneous co-injection of arrested oral fibroblasts into nude mice significantly enhanced the tumorigenicity of xenographic oral carcinoma cells. This study concludes that areca nut extract may impair oral fibroblasts and then modulate the progression of oral epithelial oncogenesis via their secreted molecules.

Key Words: areca • betel • carcinoma • fibroblast • MMP-2


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