Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells Journal Article
| Authors: | Wesley, U.; Tiwari, S.; Houghton, A. N. |
| Article Title: | Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells |
| Abstract: | Lung cancer is the leading cause of cancer death. Lung cancers produce a variety of mitogenic growth factors that stimulate tumor cell proliferation and migration. The cell surface protease, dipeptidyl peptidase IV (DPPIV), is involved in diverse biologic functions, including peptide-mediated cellular growth and differentiation. DPPIV is expressed in various normal tissues, including lung tissue, and its expression is lost in many types of human cancers. DPPIV expression and its enzymatic activity are detected in normal bronchial and alveolar epithelium but different histologic subtypes of lung carcinomas lose DPPIV expression. To investigate the role of DPPIV in lung carcinoma, we examined the expression of DPPIV at both mRNA and protein levels in non small cell lung cancer (NSCLC) cell lines and normal human bronchial epithelial cells. DPPIV expression was detectable in normal lung epitheliaI cells, but was absent or markedly reduced in all NSCLC cell lines at both mRNA and protein levels. Restoration of DPPIV expression in NSCLC cells resulted in profound morphologic changes, inhibition of cell proliferation, anchorage-independent growth, in vitro cell migration and tumorigenicity in nude mice. DPPIV reexpression also correlated with increased p21 expression, leading to induction of apoptosis and cell cycle arrest in GI stage. These effects were accompanied by increased expression of cell surface proteins, fibroblast-activating protein (Fapα) and CD44 that are associated with suppression of tumor growth and metastasis. Thus, DPPIV functions as a tumor suppressor, and its downregulation may contribute to the loss of growth control in NSCLC cells. © 2004 Wiley-Liss, Inc. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; mutation; nonhuman; cell proliferation; mouse; animals; mice; cell cycle; metastasis; apoptosis; gene expression profiling; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; animal experiment; animal model; down-regulation; membrane proteins; tumor cells, cultured; enzyme activity; mice, inbred balb c; histology; cancer inhibition; tumor suppressor gene; serine endopeptidases; nude mouse; mice, nude; messenger rna; rna, messenger; oligonucleotide array sequence analysis; carcinogenicity; cell migration; cell movement; down regulation; cyclin-dependent kinase inhibitor p21; tumor growth; bronchus mucosa; hermes antigen; cyclins; growth factor; protein p21; cell adhesion; anchorage independent growth; cell cycle g1 phase; cell surface protein; mitogenic agent; gene expression regulation, enzymologic; non small cell lung cancer; in situ nick-end labeling; antigens, cd44; gelatinases; dipeptidyl peptidase iv; lung alveolus epithelium; humans; human; priority journal; article; fibroblast activating protein alpha; antigens, cd26 |
| Journal Title: | International Journal of Cancer |
| Volume: | 109 |
| Issue: | 6 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2004-05-10 |
| Start Page: | 855 |
| End Page: | 866 |
| Language: | English |
| DOI: | 10.1002/ijc.20091 |
| PROVIDER: | scopus |
| PUBMED: | 15027119 |
| DOI/URL: | |
| Notes: | Int. J. Cancer -- Cited By (since 1996):56 -- Export Date: 16 June 2014 -- CODEN: IJCNA -- Source: Scopus |
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