Galectin-3 acts as an angiogenic switch to induce tumor angiogenesis via Jagged-1/Notch activation

Santos, Sofia Nascimento dos; Sheldon, Helen; Pereira, Jonathas Xavier; Paluch, Christopher; Bridges, Esther; El-Cheikh, Márcia Curry; Harris, Adrian L.; Bernardes, Emerson Soares

doi:10.18632/oncotarget.17718

Cited by 67 publications

(44 citation statements)

References 63 publications

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“…Since gal-3 has been shown to regulate Notch signaling activation in angiogenesis, osteoblast differentiation and dendritic cells maturation 19 – 21 , we next evaluated the expression of the Notch signaling pathway component in total bone marrow cells obtained ex vivo from Lgals3 +/+ and Lgals3 −/− mice. We observed that the expression levels of JAG1 and DLL4 ligands were increased in Lgals3 −/− mice compared with the Lgals3 +/+ mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation

Oliveira

Santos

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et al. 2018

Sci Rep

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Galectin-3 (Gal-3) is a β-galactoside binding protein that controls cell-cell and cell-extracellular matrix interactions. In lymphoid organs, gal-3 inhibits B cell differentiation by mechanisms poorly understood. The B cell development is dependent on tissue organization and stromal cell signaling, including IL-7 and Notch pathways. Here, we investigate possible mechanisms that gal-3 interferes during B lymphocyte differentiation in the bone marrow (BM) and spleen. The BM of gal-3-deficient mice (Lgals3−/− mice) was evidenced by elevated numbers of B220+CD19+c-Kit+IL-7R+ progenitor B cells. In parallel, CD45− bone marrow stromal cells expressed high levels of mRNA IL-7, Notch ligands (Jagged-1 and Delta-like 4), and transcription factors (Hes-1, Hey-1, Hey-2 and Hey-L). The spleen of Lgals3−/− mice was hallmarked by marginal zone disorganization, high number of IgM+IgD+ B cells and CD138+ plasma cells, overexpression of Notch ligands (Jagged-1, Delta-like 1 and Delta-like 4) by stromal cells and Hey-1. Morever, IgM+IgD+ B cells and B220+CD138+ CXCR4+ plasmablasts were significantly increased in the BM and blood of Lgals3−/− mice. For the first time, we demonstrated that gal-3 inhibits Notch signaling activation in lymphoid organs regulating earlier and terminal events of B cell differentiation.

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Section: Resultsmentioning

confidence: 99%

Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation

Oliveira

Santos

Ricon

et al. 2018

Sci Rep

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“…In addition to the “Warburg” profile, further examples of hypoxia-type expression regulation include upregulation of pro-angiogenic proteins such as galectin-3 [ 35 ] and MUC18 [ 36 ]. Major vault protein is known to be upregulated in hypoxia [ 37 ] and likely interacts directly with hypoxia-inducible factor (HIF)-α [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Proteome profiling of clear cell renal cell carcinoma in von Hippel-Lindau patients highlights upregulation of Xaa-Pro aminopeptidase-1, an anti-proliferative and anti-migratory exoprotease

et al. 2017

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Patients of the von Hippel-Lindau (VHL) disease frequently develop clear cell renal cell carcinoma (ccRCC). Using archived, formalin-fixed, paraffin-embedded (FFPE) samples, we sought to determine global proteome alterations that distinguish ccRCC tissue from adjacent, non-malignant kidney tissue in VHL-patients. Our quantitative proteomic analysis clearly discriminated tumor and non-malignant tissue. Significantly dysregulated proteins were distinguished using the linear models for microarray data algorithm. In the ccRCC tissue, we noticed a predominant under-representation of proteins involved in the tricarboxylic acid cycle and an increase in proteins involved in glycolysis. This profile possibly represents a proteomic fingerprint of the “Warburg effect”, which is a molecular hallmark of ccRCC. Furthermore, we observed an increase in proteins involved in extracellular matrix organization. We also noticed differential expression of many exoproteases in the ccRCC tissue. Of particular note were opposing alterations of Xaa-Pro Aminopeptidases-1 and -2 (XPNPEP-1 and -2): a strong decrease of XPNPEP-2 in ccRCC was accompanied by abundant presence of the related protease XPNPEP-1. In both cases, we corroborated the proteomic results by immunohistochemical analysis of ccRCC and adjacent, non-malignant kidney tissue of VHL patients. To functionally investigate the role of XPNPEP-1 in ccRCC, we performed small-hairpin RNA mediated XPNPEP-1 expression silencing in 786-O ccRCC cells harboring a mutated VHL gene. We found that XPNPEP-1 expression dampens cellular proliferation and migration. These results suggest that XPNPEP-1 is likely an anti-target in ccRCC. Methodologically, our work further validates the robustness of using FFPE material for quantitative proteomics.

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“…Many factors and pathways have been shown to be important in the regulation of angiogenesis (Casella et al, 2002;Kitamura et al, 2007;Acar et al, 2012;Yang et al, 2017;Ni et al, 2019). Notch-1 is a well-known factor that can alter the level of angiogenesis in various diseases including rheumatoid arthritis (Gao et al, 2012), cancer (Dos Santos et al, 2017;Jin et al, 2017), and psoriasis (Rooney et al, 2014) by regulating downstream genes.…”

Section: Introductionmentioning

confidence: 99%

LncRNA Xist Contributes to Endogenous Neurological Repair After Chronic Compressive Spinal Cord Injury by Promoting Angiogenesis Through the miR-32-5p/Notch-1 Axis

Cheng

et al. 2020

Front. Cell Dev. Biol.

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Endogenous repair after chronic compressive spinal cord injury (CCSCI) is of great clinical interest. Ischemia-hypoxia-induced angiogenesis has been proposed to play an important role during this repair process. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathophysiological processes of various diseases. Here, we identified a lncRNA (Xist; X-inactive specific transcript) with upregulated expression in cervical spine lesions during endogenous neurological repair in CCSCI rats. Therapeutically, the introduction of Xist to rats increased neurological function in vivo as assayed using the Basso, Beattie, and Bresnahan (BBB) score and inclined plane test (IPT). We found that the introduction of Xist enhanced endogenous neurological repair by promoting angiogenesis and microvessel density after CCSCI, while depletion of Xist inhibited angiogenesis and cell sprouting and migration. Mechanistically, Xist promoted angiogenesis by sponging miR-32-5p and modulating Notch-1 expression both in vitro and in vivo. These findings suggest a role of the Xist/miR-32-5p/Notch-1 axis in endogenous repair and provide a potential molecular target for the treatment of ischemia-related central nervous system (CNS) diseases.

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Galectin-3 acts as an angiogenic switch to induce tumor angiogenesis via Jagged-1/Notch activation

Cited by 67 publications

References 63 publications

Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation

Lack of galectin-3 modifies differentially Notch ligands in bone marrow and spleen stromal cells interfering with B cell differentiation

Proteome profiling of clear cell renal cell carcinoma in von Hippel-Lindau patients highlights upregulation of Xaa-Pro aminopeptidase-1, an anti-proliferative and anti-migratory exoprotease

LncRNA Xist Contributes to Endogenous Neurological Repair After Chronic Compressive Spinal Cord Injury by Promoting Angiogenesis Through the miR-32-5p/Notch-1 Axis

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