Metastatic dissemination of human malignant oral keratinocyte cell lines following orthotopic transplantation reflects response to TGF‐β 1
- 8 July 2004
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 203 (4) , 927-932
- https://doi.org/10.1002/path.1603
Abstract
This study examined the behaviour of nine human malignant oral keratinocyte cell lines following orthotopic transplantation to the floor of the mouth of athymic mice. Tumourigenesis, local spread, and metastatic dissemination were correlated with known cellular responses to transforming growth factor‐β 1 (TGF‐β 1). Six of nine cell lines were tumourigenic; four of these cell lines showed local spread which was characterized by vascular and bone invasion. Metastatic spread was uncommon, with only 9% of animals with primary tumours developing metastases and these were almost exclusively found in the regional lymph nodes; there was one pulmonary metastasis and no liver deposits. Tumour cell behaviour did not reflect the clinical stage of the original tumours. Cell lines that were resistant to TGF‐β 1‐induced growth inhibition were more likely to form primary tumours, exhibit local spread, and metastasize than cells that were growth‐inhibited by the ligand. The data demonstrate that tumourigenicity and tumour behaviour in this orthotopic mouse model varied between cell lines and that the pattern of local invasion and metastasis was similar to that seen in human oral cancer. Furthermore, cell lines that were refractory to the growth inhibitory effects of TGF‐β 1 behaved more aggressively than cells that underwent ligand‐induced cell‐cycle arrest. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Keywords
This publication has 36 references indexed in Scilit:
- Loss of differentiation of 4NQO-induced rat malignant oral keratinocytes correlates with metastatic dissemination and is associated with a reduced cellular response to TGF-pi and an altered receptor profileJournal of Oral Pathology & Medicine, 2008
- Attenuated type II TGF‐β receptor signalling in human malignant oral keratinocytes induces a less differentiated and more aggressive phenotype that is associated with metastatic disseminationInternational Journal of Cancer, 2004
- TGF-β1 acts as a tumor suppressor of human malignant keratinocytes independently of Smad 4 expression and ligand-induced G1 arrestOncogene, 2002
- TGF-β signaling: positive and negative effects on tumorigenesisCurrent Opinion in Genetics & Development, 2002
- Novel inactivating mutations of transforming growth factor-? type I receptor gene in head-and-neck cancer metastasesInternational Journal of Cancer, 2001
- Analysis of TGF-β type I receptor for mutations and polymorphisms in head and neck cancersMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 2001
- Establishment of an oral squamous cell carcinoma cell line(NOS-1) exhibiting amplification of the erbB-1 oncogene and point mutation of p53 tumor suppressor gene: its biological characteristics and animal model of local invasion by orthotopic transplantationof the cell lineOral Oncology, 2001
- Differential Expression of Cytokeratin after Orthotopic Implantation of Newly Established Human Tongue Cancer Cell Lines of Defined Metastatic AbilityThe American Journal of Pathology, 2000
- Isolation of a highly metastatic cell line to lymph node in human oral squamous cell carcinoma by orthotopic implantation in nude miceOral Oncology, 1998
- Importance of orthotopic implantation for human tumors as model systems: relevance to metastasis and invasionClinical & Experimental Metastasis, 1993