Platelet-activating factor (PAF) is the effector of IFNγ-stimulated invasiveness and motility in a B16 melanoma line

Fallani, Anna; Calorini, Lido; Mannini, Antonella; Gabellieri, Silvia; Mugnai, Gabriele; Ruggieri, Salvatore

doi:10.1016/j.prostaglandins.2006.09.004

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…C1P is formed by ceramide kinase and has been shown to oppose the apoptotic effects of ceramide and promote cell proliferation and survival through activating intracellular signaling pathways such as MEK, ERK, PI3K/AKT, and JNK, activate inflammatory responses by activating cytosolic phospholipase A2 for generating pro-inflammatory prostaglandins, and stimulate cell migration through stimulating a yet unknown extracellular G i -coupled receptor 11c . PAF, an inflammatory lipid that acts through PAF receptors and causes inflammation and platelet aggregation, has also been shown to be produced by melanoma cancer cells and promote invasiveness and metastasis through stimulating cancer cell PAF receptors in an autocrine mechanism 14 . LPA is a potent oncogenic signaling lipid that acts through stimulating LPA receptors leading to activation of multiple downstream effector pathways including phospholipase C, PI3K-AKT, RAS-ERK, and RHO and RAC GTPases leading to proliferation, survival, migration, invasion, and increased endothelial permeability 11a .…”

Section: Discussionmentioning

confidence: 99%

Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids

Louie

Roberts

Mulvihill

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

125

110

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De novo lipogenesis is considered the primary source of fatty acids for lipid synthesis in cancer cells, even in the presence of exogenous fatty acids. Here, we have used an isotopic fatty acid labeling strategy coupled with metabolomic profiling platforms to comprehensively map palmitic acid incorporation into complex lipids in cancer cells. We show that cancer cells and tumors robustly incorporate and remodel exogenous palmitate into structural and oncogenic glycerophospholipids, sphingolipids, and ether lipids. We also find that fatty acid incorporation into oxidative pathways is reduced in aggressive human cancer cells, and instead shunted into pathways for generating structural and signaling lipids. Our results demonstrate that cancer cells do not solely rely on de novo lipogenesis, but also utilize exogenous fatty acids for generating lipids required for proliferation and protumorigenic lipid signaling.

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Section: Discussionmentioning

confidence: 99%

Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids

Louie

Roberts

Mulvihill

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

125

110

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“…In the present study, we explored the possibility that MMP-2, MMP-9 and uPA system are the effectors of the enhanced invasiveness expressed by B16 murine melanoma cells stimulated with IFNc, that we reported in a previous paper [20]. We also investigated whether the enhancement of invasive properties observed in B16 melanoma cells stimulated by activated macrophages [15] is related to a release of MMP-2, MMP-9 and uPA system by these latter.…”

Section: Introductionmentioning

confidence: 94%

Tumoral and macrophage uPAR and MMP-9 contribute to the invasiveness of B16 murine melanoma cells

Marconi

Bianchini

Mannini

et al. 2007

Clin Exp Metastasis

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The aim of this study was to investigate whether tumor cells as well as tumor-associated macrophages (TAMs) contribute to the generation of protease activities essential to tumor cell invasiveness, such as matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9), and the urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR). We found that the enhanced invasiveness through Matrigel-coated filters of B16 murine melanoma cells stimulated with IFNc was associated with an higher expression of uPAR and MMP-9 in these cells. Moreover, treatment with anti-MMP-9 or anti-uPAR monoclonal antibodies abrogated the increase of invasiveness in IFNcstimulated melanoma cells, suggesting a cooperation of uPA system and MMP-9 in cytokine-stimulated invasiveness. Invasiveness through Matrigel was also enhanced in B16 melanoma cells exposed to a medium conditioned by TAMs, represented in our experimental model by thioglycollate-elicited macrophages co-cultivated with melanoma cells. Macrophages isolated from these co-cultures were found to express higher levels of uPAR and MMP-9 compared to macrophage cultures alone, and the pro-invasive activity of the co-culture-conditioned medium was abrogated by anti-MMP-9 monoclonal antibodies, but not anti-uPAR monoclonal antibodies. Furthermore, the enhanced uPAR and MMP-9 expression in macrophages cocultivated with tumor cells seems a rather specific phenomenon, generated through a cell-to-cell contact mechanism. On the whole, our data point to a cooperation between tumor cells and macrophages elicited by tumor cells themselves in generating key enzymes essential in the promotion of tumor invasiveness, such as uPAR and MMP-9.Keywords Murine melanoma cells Á Macrophages Á Cell invasiveness Á Matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) Á Urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR)

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“…Indeed, it was reported that inhibition of PAF activity by means of overexpressing PAF-acetyl-hydrolase in B16F10 murine melanoma cells led to a significant decrease in tumor vascularization and growth, allowing longer animal survival [109]. Most recently, Fallani et al have demonstrated that PAF is being synthesized by B16F10 cells in response to INF-γ treatment, and that PAF promoted the invasion of these cells through the Matrigel-coated filters [110]. Moreover, it has been shown that a single intraperitoneal injection of PAF induced expression of MMP-9 and MMP-2 in the mouse lungs, and significantly enhanced B16F10 pulmonary lung metastasis, suggesting an addition, non-tumor-cell mechanism of PAF action [111].…”

Section: Paf and Paf Receptor In Melanomamentioning

confidence: 99%

Inflammation and melanoma growth and metastasis: The role of platelet-activating factor (PAF) and its receptor

Melnikova

Bar‐Eli

2007

Cancer Metastasis Rev

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An inflammatory tumor microenvironment fosters tumor growth, angiogenesis and metastatic progression. Platelet-activating factor (PAF) is an inflammatory biolipid produced from membrane glycerophospholipids. Through the activity of its G-protein coupled receptor, PAF triggers a variety of pathological reactions including tumor neo-angiogenesis. Several groups have demonstrated that inhibiting PAF-PAF receptor pathway at the level of a ligand or receptor results in an effective inhibition of experimental tumor growth and metastasis. In particular, our group has recently demonstrated that PAF receptor antagonists can effectively inhibit the metastatic potential of human melanoma cells in nude mice. Furthermore, we showed that PAF stimulated the phosphorylation of CREB and ATF-1 in metastatic melanoma cells, which resulted in overexpression of MMP-2 and MT1-MMP. Our data indicate that PAF acts as a promoter of melanoma metastasis in vivo. Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that these cells are better equipped to respond to PAF within the tumor microenvironment when compared to their non-metastatic counterparts.

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Platelet-activating factor (PAF) is the effector of IFNγ-stimulated invasiveness and motility in a B16 melanoma line

Cited by 9 publications

References 36 publications

Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids

Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids

Tumoral and macrophage uPAR and MMP-9 contribute to the invasiveness of B16 murine melanoma cells

Inflammation and melanoma growth and metastasis: The role of platelet-activating factor (PAF) and its receptor

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