Overexpression of CC10 modifies neoplastic potential in lung cancer cells.
CC10 is infrequently expressed in non-small cell lung cancer cell lines, despite being abundantly produced by progenitor cells for normal and neoplastic airway epithelium. We overexpressed CC10 cDNA in the non-small cell lung cancer cell line A549 to determine its effect on the neoplastic phenotype. A549 cells transfected with CC10 demonstrated a marked reduction in invasiveness that was paralleled by diminished 92-kDa and absent 72-kDa metalloproteinase activity by zymography. Western analysis revealed the near absence of the corresponding matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the CC10-transfected cell lines, but not in the vector-transfected cell lines. The CC10-transfected cell lines also demonstrated decreased adhesiveness to fibronectin compared with the controls. CC10 expression was associated with decreased anchorage-independent growth but not with decreased anchorage-dependent growth. These data suggest that loss of CC10 may contribute to carcinogenesis, because CC10 antagonizes the neoplastic phenotype.
Szabo
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Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850, USA. szaboe@bprb.nci.nih.gov
Goheer
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A
Witschi
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H
Linnoila
R I
RI
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism*; D008647:Mesocricetus; D008666:Metalloendopeptidases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009385:Neoplastic Processes; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured; D014598:Uteroglobin
D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D011506:Proteins; D012333:RNA, Messenger; C556389:SCGB1A1 protein, human; D014598:Uteroglobin; D008666:Metalloendopeptidases