Unconventional secretion of fibroblast growth factor 2 and galectin‐1 does not require shedding of plasma membrane‐derived vesicles

Seelenmeyer, Claudia; Stegmayer, Carolin; Nickel, Walter

doi:10.1016/j.febslet.2008.03.024

Cited by 57 publications

(47 citation statements)

References 39 publications

(109 reference statements)

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“…Altogether, these data suggest that tumor cells can secrete galectin-1 to promote tumor progression. Interestingly, galectin-1 is secreted by a nonclassic pathway, and there seem to exist common features between the secretion of galectin-1 and that of bFGF, another potent proangiogenesis growth factor (30)(31)(32). Moreover, Le and colleagues found a correlation between the expression of galectin-1 and the hypoxia marker CA-IX (33,34).…”

Section: Discussionmentioning

confidence: 97%

Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity

et al. 2010

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Tumor angiogenesis is a key event in cancer progression. Here, we report that tumors can stimulate tumor angiogenesis by secretion of galectin-1. Tumor growth and tumor angiogenesis of different tumor models are hampered in galectin-1-null (gal-1 −/− ) mice. However, tumor angiogenesis is less affected when tumor cells express and secrete high levels of galectin-1. Furthermore, tumor endothelial cells in gal-1 −/− mice take up galectin-1 that is secreted by tumor cells. Uptake of galectin-1 by cultured endothelial cells specifically promotes H-Ras signaling to the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) kinase (Mek)/Erk cascade and stimulates endothelial cell proliferation and migration. Moreover, the activation can be blocked by galectin-1 inhibition as evidenced by hampered membrane translocation of H-Ras.GTP and impaired Raf/Mek/Erk phosphorylation after treatment with the galectin-1-targeting angiogenesis inhibitor anginex. Altogether, these data identify galectin-1 as a proangiogenic factor. These findings have direct implications for current efforts on galectin-1-targeted cancer therapies. Cancer Res; 70(15); 6216-24. ©2010 AACR.

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Section: Discussionmentioning

confidence: 97%

Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity

et al. 2010

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“…1C). To our knowledge, this is the first report of Lefty proteins using an exosomal pathway for extracellular release, and it extends the growing list of proteins/ growth factors employing this transport route [30][31][32][33]. Undoubtedly, proteins marked for exosomal delivery constitute part of an elaborated ''exsosomal code'' unique to the cells of their origin, which is thus far incompletely deciphered.…”

Section: Lefty Is Secreted Through An Exosomal Pathwaymentioning

confidence: 99%

Lefty Glycoproteins in Human Embryonic Stem Cells: Extracellular Delivery Route and Posttranslational Modification in Differentiation

Khalkhali‐Ellis

Galat

et al. 2016

Stem Cells and Development

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Lefty is a member of transforming growth factor-beta (TGF-b) superfamily and a potent antagonist of the TGFb/Nodal/Activin signaling pathway. Lefty is critical in sustaining self-renewal/pluripotency status, and implicated in the differentiation of embryonic stem cells (ESCs). However, emerging studies depict Lefty as a multifaceted protein involved in myriad cellular events. Lefty proteins (human Lefty A and B) are secreted glycoproteins, but their mode of secretion and the significance of their ''glycan'' moiety remain mostly unexplored. By employing an in vitro system of human ESCs (hESCs), we observed that Lefty protein(s) are encased in exosomes for extracellular release. The exosomal-and cell-associated Lefty diverge in their proteolytic processing, and possess N-glycan structures of high mannose and complex nature. Differentiation of hESCs to mesenchymal cells (MSCs) or neuronal progenitor cells (NPCs) entails distinct changes in the Lefty A/Lefty B gene(s), and protein expression. Specifically, the proteolytic cleavage and N-glycan composition of the cell-associated and exosomal Lefty differ in the differentiated progenies. These modifications affected Lefty's inhibitory effect on Nodal signaling in aggressive melanoma cells. The microheterogeneity in the processing and glycosylation of Lefty protein(s) between hESCs, MSCs, and NPCs could present efficient means of diversifying the endogenous functions of Lefty. Whether Lefty's diverse functions in embryonic patterning, as well as its diffusion range in the extracellular environment, are similarly affected remains to be determined. Our studies underscore the potential relevance of Lefty-packaged exosomes for combating debilitating diseases such as cancer.

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“…3D). In contrast, experiments by other groups using non-differentiated cells, such as CHO and HeLa, have suggested that secretion of galectins is independent of microvesicles (53,54). Interestingly, upon recognition of β -glucan, the major component of fungal cell walls, by the C-type lectin, dectin-1, macrophages secrete galectin-3 in a manner dependent on inflammasome activity and an active autophagic process, indicating release through the autophagic pathway ( …”

Section: B Release Of Galectins Into Extracellular Spacementioning

confidence: 63%

Cytosolic Galectins and Their Release and Roles as Carbohydrate-Binding Proteins in Host–Pathogen Interaction

Sato

2018

TIGG

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The glycocalyx is a layer of glycoconjugates found on the surface of both host cells and microorganisms. Information presented on some of the glycans on glycoconjugates is recognized by mammalian glycan-binding proteins, lectins, and these interactions modulate various physiological processes, including host innate immune responses. Lectins and host glycoconjugates are synthesized in the same secretory pathway. One notable exception is a family of soluble β-galactoside-binding lectins, galectins, which are synthesized and accumulated in the cytosol and thereby segregated from their glycan ligands. In cases where pathogenic infection persists and tissue injury occurs, galectins are passively released from injured cells. In addition, galectins are actively secreted through unconventional secretory pathways by inflammation-activated or differentiating cells. Thus, extracellular emergence of galectins is associated with the presence of pathogenic hazards. Evidence from a series of studies suggests that galectins exert multiple immunological effects. Extracellular galectin-3 acts as a damage-associated molecular pattern (DAMP) and adhesion molecule for neutrophils in lungs to initiate a proinflammatory response and to mediate rapid neutrophil migration in lungs infected with pathogenic microorganisms. In this review, the roles of galectin-3 in initial innate immune responses and resolution are discussed together with a historical overview of research on galectins in the secretory pathway and innate immunology. A. Galectins Accumulate in the Cytosol: Distinct Segregation from Glycan LigandsIn mammalian cells, the majority of glycans, i.e., oligosaccharides and polysaccharides, are covalently linked to either proteins Galectins are soluble, non-glycosylated lectins defined by a conserved carbohydrate recognition domain (CRD) that shows affinity for β-galactoside, especially glycans containing a number of lactosamine residues (Galβ1-4GlcNAc) (2-4). Detailed information on the carbohydrate binding specificity of galectins has been provided in the review by the group of Hirabayashi in the TIGG special issue 'Galectins updated' (5). In humans, 11 galectins have been identified to date (2). These proteins exhibit structural differences in the presentation of CRD (Fig. 1A). Some contain one CRD (prototype) and exist as either monomers or dimers while others (tandem repeats) contain two CRDs connected by a short linker region. Galectin-3 uniquely occurs as a chimeric protein with one CRD at the C-terminus and an additional non-CRD domain at the N-terminus, which is involved in its oligomerization.Upon binding to its glycan ligands, the conformation of galectin-3 appears altered. Subsequently, galectin-3 molecules oligomerize through self-assembly of the non-CRD domains and become multivalent in glycan binding (Fig. 1B) (6-12). In addition to N-terminal-mediated oligomerization, CRD of galectin-3 selfassociates upon binding to its ligands, thereby contributing to positive cooperativity in the formation of multivalency ...

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Unconventional secretion of fibroblast growth factor 2 and galectin‐1 does not require shedding of plasma membrane‐derived vesicles

Cited by 57 publications

References 39 publications

Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity

Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity

Lefty Glycoproteins in Human Embryonic Stem Cells: Extracellular Delivery Route and Posttranslational Modification in Differentiation

Cytosolic Galectins and Their Release and Roles as Carbohydrate-Binding Proteins in Host–Pathogen Interaction

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