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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-7-12
pubmed:abstractText
Chemical transformation of the SV-40 immortalized bronchial epithelial cell line BEAS2-B induces alterations in molecules involved in cell cycle control, including up-regulation of EGFR and cyclin E [Oncogene 13 (1996) 1983; Clin Cancer Res 8 (2002) 54]. The finding that these changes also occur in vivo, in both pre-invasive and invasive lung cancer [Cancer Res 55 (1995) 1365; Cancer Res 59 (1999) 2470], proves this to be a suitable model to study lung carcinogenesis. The current study tested the hypothesis that chemical treatment of BEAS2-B with Cigarette Smoke Condensate (CSC) may affect levels of gene products involved in cell adhesion and tissue remodeling. To this end, we studied the extent of changes in osteonectin (ON) protein levels induced in BEAS 2 B-cells by CSC treatment and its timing to changes occurring in the anchorage independent cloning efficiency. ON, a multimodular protein component of the extra-cellular matrix, has been implicated in tissue remodeling occurring in neoplastic and non-neoplastic conditions, but its role in lung carcinogenesis is incompletely characterized. To validate the in vitro findings, as in our previous reports, we studied resected lung tissue, to assess whether ON expression in neoplastic lung tissue differs from normal, and to determine its cellular localization. We found that CSC treatment of BEAS2-B cells results in a 7-16-fold increase in ON protein levels, that is associated with increased colony forming efficiency. ON is absent in normal lung; in contrast it is present in the majority (39/52) of non-small cell lung cancer (NSCLC). Here, its expression is restricted to peritumoral fibroblasts in squamous cell carcinoma and adenocarcinoma. In contrast, it is localized to tumor cells in pulmonary sarcomatoid carcinoma (8/10). Thus, up-regulated ON is linked in vitro to cell transformation and in vivo, it is frequently expressed in tumor-associated fibrosis, compatible with its proposed role in tissue remodelling. Increased ON expression by tumor cells appears to represent a marker of sarcomatoid NSCLC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0169-5002
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
197-205
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15246191-Biopsy, Needle, pubmed-meshheading:15246191-Blotting, Western, pubmed-meshheading:15246191-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:15246191-Case-Control Studies, pubmed-meshheading:15246191-Cell Transformation, Neoplastic, pubmed-meshheading:15246191-Cells, Cultured, pubmed-meshheading:15246191-Epithelial Cells, pubmed-meshheading:15246191-Female, pubmed-meshheading:15246191-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15246191-Humans, pubmed-meshheading:15246191-Immunohistochemistry, pubmed-meshheading:15246191-Lung Neoplasms, pubmed-meshheading:15246191-Male, pubmed-meshheading:15246191-Osteonectin, pubmed-meshheading:15246191-Probability, pubmed-meshheading:15246191-Pulmonary Fibrosis, pubmed-meshheading:15246191-Reference Values, pubmed-meshheading:15246191-Sensitivity and Specificity, pubmed-meshheading:15246191-Smoke
pubmed:year
2004
pubmed:articleTitle
Increased osteonectin expression is associated with malignant transformation and tumor associated fibrosis in the lung.
pubmed:affiliation
Laboratory of Thoracic Oncology, Wayne State University Medical School, Harper University Hospital and Karmanos Cancer Institute, Detroit, MI 48201, USA.
pubmed:publicationType
Journal Article, Comparative Study