Cell adhesion-mediated transformation of a human SCLC cell line is associated with the development of a normal phenotype.
Small cell lung carcinoma (SCLC) is a highly metastatic disease with a poor prognosis due to its resistance to current modes of therapy. SCLC cells appear to arise by oncogenic transformation of self-renewing pulmonary neuroendocrine cells, which have the potential to differentiate into a variety of lung epithelial cell lineages. Epithelial-mesenchymal conversion involved in such cell type transitions leads to the acquisition of an invasive and metastatic phenotype and may be critical for neoplastic progression and its eventual resistance to therapy. In order to investigate mechanisms involved in such transitions, a SCLC cell line was exposed to 5-bromodeoxyuridine. This treatment induced a dramatic conversion from non-substrate-adherent aggregates to monolayers of cells exhibiting an epithelioid phenotype. The phenotypic transition was concomitant with downregulation of vimentin, upregulation of cytokeratins, and cell-cell and cell-matrix adhesion molecules as well as redistribution of the actin cytoskeleton. The changes in the levels and organization of cell-cell and cell-matrix adhesion molecules were correlated with an in vivo loss of tumorigenicity.
Gilchrist
Anita J
AJ
Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.
Meuser
Renate
R
Turchinsky
Joan
J
Shaw
Andrew R E
AR
Pasdar
Manijeh
M
Dixon
Walter T
WT
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002415:Cats; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D003599:Cytoskeleton / Q000648:ultrastructure; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D004273:DNA, Neoplasm; D019012:Integrin beta1