CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells
Journal
International Journal of Cancer
Journal Volume
116
Journal Issue
2
Pages
243-252
Date Issued
2005
Author(s)
Chang Y.-W.
Chen S.-C.
Cheng E.-C.
Ko Y.-P.
Lin Y.-C.
Kao Y.-R.
Tsay Y.-G.
Wu C.-W.
Roffler S.R.
Abstract
Cancer metastasis is a multiple-step process that involves the regulated interaction of diverse cellular proteins. We recently reported that the expression of tumor-associated antigen L6 (TAL6) promoted the invasiveness of lung cancer cells and was inversely correlated with disease-free survival of squamous lung carcinoma patients. We now report that CD13 (aminopeptidase N) can associate with TAL6 and can enhance cancer cell migration. CD13 was shown by coimmunoprecipitation to associate in vitro with TAL6 on several cancer cell lines and to associate in vivo by antibody-mediated copatching immunofluorescence. CD13 was selectively expressed on highly invasive CL1-5 lung cancer cells as compared to poorly invasive CL1-0 lung cancer cells. The role of CD13 aminopeptidase activity in regulating cell motility was investigated with chemical inhibitors, specific antibodies and a catalytically inactive CD13 protein. Inhibition of CD13 aminopeptidase activity by nontoxic concentrations of leuhistin modestly decreased the migration of CL1-5 cells. In contrast, binding of CD13 by specific antibodies significantly reduced both the migration and the invasion of CL1-5 cells. Poorly invasive CL1-0 cells that stably expressed CD13 displayed significantly (p < 0.0005) enhanced cell migration (300% of control). Expression of an enzymatically inactive CD13 mutant on CL1-0 cells also significantly (p < 0.0005) enhanced cell migration (200% of control). Our results show that TAL6 and CD13 can form a complex on lung cancer cells, that these molecules can modulate cell migration and invasion and that the influence of CD13 on cell motility did not strictly depend on its aminopeptidase activity. ? 2005 Wiley-Liss, Inc.
Subjects
Aminopeptidase N; CD13; Invasion; Metastasis; Migration; Motility; TAL6; Tetraspanin; Tumor-associated antigen L6
SDGs
Other Subjects
enzyme inhibitor; leuhistin; microsomal aminopeptidase; tumor antigen; tumor associated antigen L6; unclassified drug; animal cell; antigen expression; article; cancer invasion; cancer survival; cell migration; cell motility; complex formation; controlled study; enzyme activity; enzyme inhibition; human; human cell; immunofluorescence; immunoprecipitation; lung cancer; lung squamous cell carcinoma; metastasis; mouse; nonhuman; priority journal; protein protein interaction; Adenocarcinoma; Antibodies; Antigens, CD13; Antigens, Surface; Carcinoma, Non-Small-Cell Lung; Cell Movement; Gene Expression Regulation, Neoplastic; Humans; Immunoprecipitation; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins
Type
journal article