Document Detail

Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells.
MedLine Citation:
PMID:  23207293     Owner:  NLM     Status:  MEDLINE    
The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PCa) cells is closely related to tumour progression and hormone resistance. The mechanisms by which NE cells influence PCa growth and progression are not fully understood. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in oncogenic processes, and MIF serum levels correlate with aggressiveness of PCa. Here, we investigated the regulation and the functional consequences of MIF expression during NE transdifferentiation of PCa cells. NE differentiation (NED) of LNCaP cells, initiated either by increasing intracellular levels of cAMP or by culturing cells in an androgen-depleted medium, was associated with markedly increased MIF release. Yet, intracellular MIF protein and mRNA levels and MIF gene promoter activity decreased during NED of LNCaP cells, suggesting that NED favours MIF release despite decreasing MIF synthesis. Adenoviral-mediated forced MIF expression in NE-differentiated LNCaP cells increased cell proliferation without affecting the expression of NE markers. Addition of exogenous recombinant MIF to LNCaP and PC-3 cells stimulated the AKT and ERK1/2 signalling pathways, the expression of genes involved in PCa, as well as proliferation and resistance to paclitaxel and thapsigargin-induced apoptosis. Altogether, these data provide evidence that increased MIF release during NED in PCa may facilitate cancer progression or recurrence, especially following androgen deprivation. Thus, MIF could represent an attractive target for PCa therapy.
Thomas Tawadros; Florian Alonso; Patrice Jichlinski; Noel Clarke; Thierry Calandra; Jacques-Antoine Haefliger; Thierry Roger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-02-18
Journal Detail:
Title:  Endocrine-related cancer     Volume:  20     ISSN:  1479-6821     ISO Abbreviation:  Endocr. Relat. Cancer     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-19     Completed Date:  2013-07-02     Revised Date:  2013-07-08    
Medline Journal Info:
Nlm Unique ID:  9436481     Medline TA:  Endocr Relat Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  137-49     Citation Subset:  IM    
Service of Urology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 46, Lausanne, Switzerland.
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MeSH Terms
Blotting, Northern
Blotting, Western
Cell Differentiation*
Cell Proliferation*
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Intramolecular Oxidoreductases / genetics,  metabolism*
Macrophage Migration-Inhibitory Factors / genetics,  metabolism*
Neuroendocrine Cells / metabolism,  pathology*
Prostatic Neoplasms / genetics,  metabolism,  pathology*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Reg. No./Substance:
0/Macrophage Migration-Inhibitory Factors; 0/RNA, Messenger; EC 5.3.-/Intramolecular Oxidoreductases; EC protein, human
Comment In:
Endocr Relat Cancer. 2013 Jun;20(3):C1-4   [PMID:  23612613 ]

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