Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis is a coordinated process that depends on the interaction of cancer cells with the tumor microenvironment. Members of the transmembrane-4 superfamily (TM4SF) of surface proteins have been implicated in the regulation of cancer cell metastasis, and the expression of several TM4SF members on tumor cells is inversely correlated with patient prognosis. The tumor-associated antigen L6 (TAL6), a distant member of the TM4SF, is expressed on most epithelial cell carcinomas and is a target for antibody-mediated therapy. We examined whether TAL6 may play a role in cancer metastasis by using an established series of human lung carcinoma cell lines (CL1-0 to CL1-5) that exhibit increasing invasiveness in vitro and in vivo. We found that TAL6 expression correlated with the in vitro invasiveness of CL lung carcinoma cells (r(2) = 0.98) and human carcinoma cells (r(2) = 0.69). Forced expression of TAL6 on CL1-0 lung carcinoma cells significantly increased their in vitro invasiveness and decreased the survival of SCID mice in an experimental metastasis model. Specific antibody against TAL6 (monoclonal antibody L6) significantly reduced the migration and invasiveness of CL1-5 lung carcinoma cells. The effects of monoclonal antibody L6 on CL1-5 invasion required clustering of TAL6 on the cell surface. Real-time reverse transcription-PCR of lung cancer specimens showed that increased expression of TAL6 was significantly associated with early postoperative relapse (P = 0.034) and shorter survival (P = 0.025) in squamous cell lung cancer patients. Thus, TAL6 appears to be involved in cancer invasion and metastasis.
 ...
PMID:Tumor-associated antigen L6 and the invasion of human lung cancer cells. 1285 61

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 < or = 0.0005) enhanced cell migration (300% of control). Expression of an enzymatically inactive CD13 mutant on CL1-0 cells also significantly (p < or = 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.
 ...
PMID:CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells. 1581 28