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A lymph node metastatic mouse model reveals alterations of metastasis-related gene expression in metastatic human oral carcinoma sublines selected from a poorly metastatic parental cell line
Article first published online: 3 OCT 2002
Copyright © 2002 American Cancer Society
Volume 95, Issue 8, pages 1663–1672, 15 October 2002
How to Cite
Zhang, X., Liu, Y., Gilcrease, M. Z., Yuan, X. H., Clayman, G. L., Adler-Storthz, K. and Chen, Z. (2002), A lymph node metastatic mouse model reveals alterations of metastasis-related gene expression in metastatic human oral carcinoma sublines selected from a poorly metastatic parental cell line. Cancer, 95: 1663–1672. doi: 10.1002/cncr.10837
- Issue published online: 3 OCT 2002
- Article first published online: 3 OCT 2002
- Manuscript Accepted: 25 JUN 2002
- Manuscript Revised: 1 MAR 2002
- Manuscript Received: 19 DEC 2001
- NIH Research Career Development Award. Grant Number: K02 DE00426 (Z.C.)
- The University Cancer Foundation at The University of Texas M. D. Anderson Cancer Center (Z.C.)
- NIH Cancer Center. Grant Number: NCI-CA16672
- matrix metalloproteinase-2;
- matrix metalloproteinase-9;
- membrane type 1-matrix metalloproteinase;
- urokinase-type plasminogen activator receptor;
- protease-activated receptor-1;
- squamous cell carcinoma
Greater than 40% of patients with squamous cell carcinoma (SCC) of the oral cavity have lymph node metastasis at the time of diagnosis and a 5-year survival rate of less than 50%. Changes in gene expression that regulate metastasis of SCC to lymph nodes have not been identified.
To study metastasis of oral SCC, highly metastatic oral SCC cell lines from a poorly metastatic oral SCC cell line were established by in vivo selection using a lymph node metastatic mouse model. The metastatic potential of the cells was studied using Matrigel invasion and cell surface protein adhesion assays. mRNA and protein encoded from metastasis-related genes in the metastatic derivatives and in their parental cells were examined using Northern blot analysis, immunoblotting, rapid analysis of gene expression, and a cDNA microarray technique.
The in vivo selected metastatic cells showed much higher Matrigel invasion capability than the parental cells. They also showed alterations in their adhesion properties to three cell surface proteins. Comparison of metastatic and nonmetastatic cells revealed several significant alterations in the expression of metastasis-related genes, including up-regulation of the urokinase-type plasminogen activator receptor, integrin β1, membrane type 1-matrix metalloproteinase, and down-regulation of protease-activated receptor-1.
To the authors' knowledge, the current study is the first to report on gene expression analysis using a lymph node metastatic mouse model of human oral SCC. The data suggest that certain alterations of metastasis-related gene expression favor invasion of oral SCC and that cell surface proteins may play major roles in the metastasis of oral SCC to the lymph nodes. Cancer 2002;95:1663–72. © 2002 American Cancer Society.