Document Detail

Selective upregulated expression of the alpha2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells.
MedLine Citation:
PMID:  11097186     Owner:  NLM     Status:  MEDLINE    
Cellular binding of receptor-recognized forms of alpha2-macroglobulin (alpha2M*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). In nonmalignant cells, ligation of alpha2MSR promotes DNA synthesis and cellular proliferation. Here, we report that insulin treatment of highly metastatic 1-LN human prostate carcinoma selectively increases alpha2MSR expression and binding of alpha2M* to 1-LN cells. alpha2M* induces transient increases in intracellular calcium and inositol 1,4,5-trisphosphate in insulin-treated 1-LN cells, consistent with activation of alpha2MSR. Inhibition of signaling cascades activated by insulin blocks upregulation of alpha2MSR. By contrast, alpha2M* does not bind to nor induce intracellular signaling in PC-3 cells, even though 1-LN cells were subcloned from PC-3 cells. We suggest that alpha2M* behaves like a growth factor in these highly malignant cells. The 1-LN metastatic phenotype may result, in part, from aberrant expression of alpha2MSR, indicating the possible involvement of alpha2M* in tumor progression.
I R Asplin; U K Misra; G Gawdi; M Gonzalez-Gronow; S V Pizzo
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  383     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-12     Completed Date:  2000-12-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  135-41     Citation Subset:  IM    
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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MeSH Terms
Hypoglycemic Agents / pharmacology*
Insulin / pharmacology*
LDL-Receptor Related Protein 1
Neoplasm Invasiveness
Neoplasm Metastasis
Prostatic Neoplasms / metabolism*,  pathology
RNA, Messenger / biosynthesis
Receptors, Immunologic / biosynthesis*
Signal Transduction / drug effects
Tumor Cells, Cultured
Up-Regulation / drug effects
alpha-Macroglobulins / metabolism*
Grant Support
Reg. No./Substance:
0/Hypoglycemic Agents; 0/LDL-Receptor Related Protein 1; 0/RNA, Messenger; 0/Receptors, Immunologic; 0/alpha-Macroglobulins; 11061-68-0/Insulin

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