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(American Journal of Pathology. 2000;156:1317-1326.)
© 2000 American Society for Investigative Pathology

Regular Articles

Differential Expression of Cytokeratin after Orthotopic Implantation of Newly Established Human Tongue Cancer Cell Lines of Defined Metastatic Ability

Masayo Morifuji^*, Shun’ichiro Taniguchi^¶, Hidetaka Sakai, Yusaku Nakabeppu^§ and Masamichi Ohishi^*

From the First Department of Oral and Maxillofacial Surgery^*
and Oral Pathology,
Faculty of Dentistry, Kyushu University, Fukuoka; the Department of Biochemistry,
Medical Institute of Bioregulation, Kyushu University, Fukuoka; CREST,^§
Japan Science and Technology Corporation, Fukuoka; and the Department of Molecular Oncology and Angiology,^¶
Research Center on Aging and Adaptation, Shinsyu University School of Medicine, Matsumoto, Japan

Two human tongue squamous cell carcinoma cell lines, SQUU-A and SQUU-B, were established from the same patient. Cervical lymph node metastasis was detected in the mice orthotopically implanted with SQUU-B (86.7%, 13/15), but not in those with SQUU-A (0/13). Histologically, SQUU-B showed invasive growth and intravasation in the tongue, whereas SQUU-A simply demonstrated expansive growth without intravasation. By Western blot analysis, nonmetastatic clone SQUU-A expressed cytokeratin (CK)13/4, 14, 16/6, 18/8, and 19, whereas a high metastatic clone SQUU-B expressed CK18/8 and 19. The reverse transcription-polymerase chain reaction technique showed that CK13/4 mRNA was expressed in both cell lines, but CK14 and 16 mRNA was expressed only in SQUU-A. CK13 was immunohistochemically expressed in both SQUU-A and SQUU-B transplanted into the tongues of nude mice; CK14 and 16 were detected in SQUU-A of the tongues, but not in SQUU-B. As seen in SQUU-B cell line, SQUU-B of the cervical lymph node metastasis did not exhibit CK13, 14, or 16. These results suggest that the loss or down-regulation of CK13, 14, or 16 is related to the invasive and metastatic ability of cancer. The cytoskeletal system is thus considered to be closely related to the malignant phenotype.

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