Role of tumor-associated gangliosides in cancer progression

Birklé, Stéphane; Zeng, Guichao; Gao, Lan; Yu, Robert K.; Aubry, Jacques

doi:10.1016/s0300-9084(03)00006-3

Cited by 213 publications

(173 citation statements)

References 70 publications

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“…Under physiological conditions, gangliosides are mainly associated to the membrane of different cell types, including endothelium, where they modulate cell growth, adhesion, and cell-cell interaction [144]. During tumor growth and metastatization, gangliosides shed in the microenvironment [145] with a consequent increase of their serum levels (Table 1) and accumulation in the tumor microenvironment.…”

Section: Gangliosidesmentioning

confidence: 99%

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Presta

Dell’Era

Mitola

et al. 2005

Cytokine & Growth Factor Reviews

1,120

870

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Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors. FGFs exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Their activity is modulated by a variety of free and extracellular matrix-associated molecules. Also, the cross-talk among FGFs, vascular endothelial growth factors (VEGFs), and inflammatory cytokines/chemokines may play a role in the modulation of blood vessel growth in different pathological conditions, including cancer. Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization. #

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Section: Gangliosidesmentioning

confidence: 99%

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Presta

Dell’Era

Mitola

et al. 2005

Cytokine & Growth Factor Reviews

1,120

870

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“…These molecules show large quantitative and structural variability, which is related to cell type and developmental stage. There are several functional roles of gangliosides in tumor progression: they act as immunosuppressors, as observed for the suppression of cytotoxic T cells and dendritic cells; certain gangliosides, such as GD3 or GM2, promote tumor-associated angiogenesis; gangliosides strongly regulate cell adhesion/motility and thus initiate tumor metastasis; ganglioside antigens and their catabolites are modulators of signal transduction through interaction with tyrosine kinases associated with growth factor receptors or other protein kinases (Birkle et al, 2003). Most tumors exhibit aberrant ganglioside expression.…”

Section: Differentiation Antigensmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

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“…Gangliosides are sialic acid-containing membrane glycosphingolipids, which regulate tumor invasion, metastasis, and growth by modulating signal transduction at the plasma membrane (4)(5)(6). Alterations of ganglioside expression and distribution in malignant tumors correlate with their features of abnormal cell growth, associated inflammation, and oncogenic transformation (4,6,7).…”

Section: Introductionmentioning

confidence: 99%

Deacetylated GM3 Promotes uPAR-Associated Membrane Molecular Complex to Activate p38 MAPK in Metastatic Melanoma

Qiu

Bach

Gatla

et al. 2013

Molecular Cancer Research

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GM3, the simplest ganglioside, regulates cell proliferation, migration, and invasion by influencing cell signaling at the membrane level. Although the classic N-acetylated form of GM3 (NeuAcLacCer) is commonly expressed and has been well studied, deacetylated GM3 (NeuNH 2 LacCer, d-GM3) has been poorly investigated, despite its presence in metastatic tumors but not in noninvasive melanomas or benign nevi. We have recently found that d-GM3 stimulates cell migration and invasion by activating urokinase plasminogen activator receptor (uPAR) signaling to augment matrix metalloproteinase-2 (MMP-2) function. However, the mechanisms by which d-GM3/ uPAR increase MMP-2 expression and activation are not clear. By modifying the expression of d-GM3 genetically and biochemically, we found that decreasing d-GM3 expression inhibits, whereas overexpressing d-GM3 stimulates, p38 mitogen-activated protein kinase (MAPK) activity to influence MMP-2 expression and activation. p38 MAPK (p38) activation requires the formation of a membrane complex that contains uPAR, caveolin-1, and integrin a5b1 in membrane lipid rafts. In addition, knocking down or inhibiting focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), or Src kinase significantly reduces d-GM3-induced p38 phosphorylation and activation. Taken together, these results suggest that d-GM3 enhances the metastatic phenotype by activating p38 signaling through uPAR/integrin signaling with FAK, PI3K, and Src kinase as intermediates. Elucidation of the mechanisms by which d-GM3, a newly discovered, potential biomarker of metastatic melanomas, promotes cell metastasis will help us to understand the function of d-GM3 in metastatic melanomas and may lead to novel GM3-based cancer therapies. Mol Cancer Res; 11(6); 665-75. Ó2013 AACR. IntroductionAlthough recent therapeutic progress for metastatic melanomas has significantly improved, including the more recent availability of small-molecule inhibitors targeting BRAF mutation or both BRAF mutation and MEK, or anti-CTLA4 antibody, survival is minimally prolonged and mortality rate of metastatic melanomas remains high (1-3). It is of utmost importance to discover specific molecular biomarkers that can distinguish melanomas with metastatic propensity from more indolent ones, which will improve prognostication, allow for earlier and more efficacious treatments, and provide additional targets for novel therapy.

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Role of tumor-associated gangliosides in cancer progression

Cited by 213 publications

References 70 publications

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Novel antibodies as anticancer agents

Deacetylated GM3 Promotes uPAR-Associated Membrane Molecular Complex to Activate p38 MAPK in Metastatic Melanoma

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