The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion

BMC Cancer

Research Article

Angeles Garcia-Pardo¹  Yvonne L Kapila²  Nisha J D'Silva²  Pachiyappan Kamarajan² 

[1] Cellular and Molecular Medicine Program, Centro de Investigaciones Biologicas, CSIC, Madrid, Spain;Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 48109-1078, Ann Arbor, Michigan, USA;

关键词: Focal Adhesion Kinase;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma Cell;    Oral Squamous Cell Carcinoma Cell Line;   

DOI  :  10.1186/1471-2407-10-330

 received in 2009-08-20, accepted in 2010-06-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe alternatively spliced V region or type III connecting segment III (IIICS) of fibronectin is important in early development, wound healing, and tumorigenesis, however, its role in oral cancer has not been fully investigated. Thus, we investigated the role of CS-1, a key site within the CSIII region of fibronectin, in human oral squamous cell carcinoma (OSCC).MethodsTo determine the expression of CS-1 in human normal and oral SCC tissue specimens immunohistochemical analyses were performed. The expression of CS1 was then associated with clinicopathological factors. To investigate the role of CS-1 in regulating OSCC cell spreading, migration and invasion, OSCC cells were assayed for spreading and migration in the presence of a CS-1 peptide or a CS-1 blocking peptide, and for invasion using Matrigel supplemented with these peptides. In addition, integrin α4siRNA or a focal adhesion kinase (FAK) anti-sense oligonucleotide was transfected into OSCC cells to examine the mechanistic role of integrin α4 or FAK in CS1-mediated cell spreading and migration, respectively.ResultsCS-1 expression levels were significantly higher in OSCC tissues compared to normal tissues (p < 0.05). Also, although, high levels of CS-1 expression were present in all OSCC tissue samples, low-grade tumors stained more intensely than high grade tumors. OSCC cell lines also expressed higher levels of CS-1 protein compared to normal human primary oral keratinocytes. There was no significant difference in total fibronectin expression between normal and OSCC tissues and cells. Inclusion of CS-1 in the in vitro assays enhanced OSCC cell spreading, migration and invasion, whereas the CS1 blocking peptide inhibited these processes. Suppression of integrin α4 significantly inhibited the CS1-mediated cell spreading. Furthermore, this migration was mediated by focal adhesion kinase (FAK), since FAK suppression significantly blocked the CS1-induced cell migration.ConclusionThese data indicate that the CS-1 site of fibronectin is involved in oral cancer pathogenesis and in regulating OSCC cell spreading, migration and invasion.

【 授权许可】

Unknown   
© Kamarajan et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.