186 Progression/Metastasis of Xenografted Oral Cancer Cell-lines in Mouse Tongue

Thursday, March 22, 2012: 10:45 a.m. - 12:15 p.m.
Presentation Type: Oral Session
Y. SOENO1, Y. SHIRAKO1, K. FUJITA1, Y. TAYA1, Y. SHIMAZU1, K. NAKAU1, K. SATO1, T. CHIBA2, K. IMAI2, and T. AOBA1, 1Dept. of Pathology, Nippon Dental Univeristy, Tokyo, Japan, 2Dept. of Biochemistry, Nippon Dental University, Tokyo, Japan
Objectives: Oral squamous cell carcinoma (SCC) in tongue exhibits rapid progression into the surrounding stroma and is prone to metastasize to regional lymph-nodes. The invasion, metastasis and prognosis of SCC are determined in part by the communication between cancer cells and surrounding microenvironment. The present study aimed to elucidate the tumor-stroma interaction using a mouse xenograft model with focus on the EMT-like phenotypic modulation of tumor cells as monitored by a coupling of E-cadherin downregulation and vimentin upregulation. Methods: Five oral SCC cell-lines (KOSC2, HO-1u1, HSC2, OSC19, and OSC20) were used. Each cell line grown in culture was transplanted (2x105 cells) into a BALB/c nude-mouse tongue. A whole tongue and regional neck lymph-nodes were dissected from the animals at periodical intervals after inoculation and then processed for preparation of paraffin-embedded serial sections (4µm thick). Phenotypic alterations of cancer cells at the primary sites and lymph-nodes were examined by immunohistochemistry and gene expression analysis. Results: Although all cell-lines gave rise formed visible tumor masses (2mm or larger) in the tongue within 2 to 3 weeks, the individual cell-lines showed a marked diversity with respect to proliferation activity measured by MIB1-positive number, induction of blood/lymph vessels, and EMT-like phenotypic alterations. The mode of local invasion was divided into two types: cell-lines with high proliferation exhibited expansive invasion by replacing the muscle tissue, whereas cell-lines with modest proliferation had a tendency to expand through gaps between muscle fibers. Four cell-lines except for KOSC2 were validated to induce lymph-node metastasis. Conclusions: The results obtained support the contention that the progression and regional metastasis of SCC were correlated with the proliferation activity of tumor cells and the angio/lymphangiogenesis in the microenvironment, but the EMT-like phenotypic alteration appears not to be prerequisite for the local progression and regional metastasis.

Keywords: Animal, Carcinogenesis, Gene expression, Pathology and Tongue
See more of: Carcinogenesis I
See more of: Oral Medicine & Pathology
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