scholarly journals Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells

2012 ◽  
Vol 20 (1) ◽  
pp. 137-149 ◽  
Author(s):  
Thomas Tawadros ◽  
Florian Alonso ◽  
Patrice Jichlinski ◽  
Noel Clarke ◽  
Thierry Calandra ◽  
...  

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 andMIFgene 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.

2005 ◽  
Vol 173 (4S) ◽  
pp. 382-382
Author(s):  
Katherine L. Meyer-Siegler ◽  
Kenneth A. Iczkowski ◽  
Lin Leng ◽  
Richard Bucala ◽  
Pedro L. Vera

2013 ◽  
Vol 20 (3) ◽  
pp. C1-C4 ◽  
Author(s):  
Rosalinda M Savoy ◽  
Paramita M Ghosh

A new paper by Tawadroset al. inEndocrine-Related Cancerdemonstrates a link between macrophage migration inhibitory factor and neuroendocrine differentiation in prostate cancer. This paper may have implications in explaining the effect of prostatitis and chronic inflammation on the development of aggressive prostate cancer.


2011 ◽  
Vol 32 (8) ◽  
pp. 2307-2311 ◽  
Author(s):  
Mara Anaís Llamas-Covarrubias ◽  
Yeminia Valle ◽  
Rosa Elena Navarro-Hernández ◽  
Iris Paola Guzmán-Guzmán ◽  
María Guadalupe Ramírez-Dueñas ◽  
...  

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6037-6042 ◽  
Author(s):  
Daisuke Ikeda ◽  
Shinji Sakaue ◽  
Mitsunori Kamigaki ◽  
Hiroshi Ohira ◽  
Naofumi Itoh ◽  
...  

Obesity is a condition in which adipose tissue mass is expanded. Increases in both adipocyte size and number contribute to enlargement of adipose tissue. The increase in cell number is thought to be caused by proliferation and differentiation of preadipocytes. Macrophage migration inhibitory factor (MIF) is expressed in adipocytes, and intracellular MIF content is increased during adipogenesis. Therefore, we hypothesized that MIF is associated with adipocyte biology during adipogenesis and focused on the influence of MIF on adipogenesis. To examine the effects of MIF on adipocytes, MIF expression in 3T3-L1 preadipocytes was inhibited by RNA interference, and cell differentiation was induced by standard procedures. The triglyceride content of MIF small interfering RNA (siRNA)-transfected 3T3-L1 cells was smaller than that of nonspecific siRNA-transfected cells. In addition, MIF knockdown apparently abrogated increases in adiponectin mRNA levels during differentiation. Gene expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP)α, and C/EBPδ decreased with MIF siRNA transfection, but C/EBPβ expression increased. Cell number and incorporation of 5-bromo-2-deoxyuridine into cells decreased from 1–3 d and from 14–20 h, respectively, after induction of differentiation in MIF siRNA-transfected cells, thus suggesting that MIF siRNA inhibits mitotic clonal expansion. Taken together, these results indicated that MIF regulates differentiation of 3T3-L1 preadipocytes, at least partially, through inhibition of mitotic clonal expansion and/or C/EBPδ expression.


PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e57181 ◽  
Author(s):  
Romina A. Cutrullis ◽  
Patricia B. Petray ◽  
Edgardo Schapachnik ◽  
Rubén Sánchez ◽  
Miriam Postan ◽  
...  

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