The Animal Lectin Galectin-8 Promotes Cytokine Expression and Metastatic Tumor Growth in Mice

Shatz-Azoulay, Hadas; Vinik, Yaron; Isaac, Roi; Köhler, Ulrike A.; Lev, Sima; Zick, Yehiel

doi:10.1038/s41598-020-64371-z

Cited by 24 publications

(40 citation statements)

References 62 publications

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“…This finding demonstrates the possible synergistic effects of different components of the extracellular matrix, which may play important roles in cell adhesion and migration in vivo. In particular, since formation of filopodia was shown to correlate with cancer cell metastasis(Arjonen et al, 2011;Jacquemet et al, 2015), our results could explain why excessive production of galectin-8 augments the metastatic capacity of cancer cells(Gentilini et al, 2017;Reticker-Flynn et al, 2012;Shatz-Azoulay et al, 2020).…”

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confidence: 75%

Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates

Sancho

Chung

et al. 2021

Journal of Cell Science

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The mechanisms underlying the cellular response to extracellular matrices (ECM), consisting of multiple adhesive ligands, are still poorly understood. Here we address this topic by monitoring the differential cellular response to two different extracellular adhesion molecules – fibronectin, a major integrin ligand, and galectin-8, a lectin, that binds β-galactoside residues, as well as to mixtures of the two proteins. Cell spreading on galectin-8 coated substrates results in a larger projected cell area, a more extensive extension of filopodia, yet an inability to form focal adhesions and stress fibers, compared to cell spreading on fibronectin. These differences can be partially reversed by experimental manipulations of small G-proteins of the Rho family and their downstream targets, such as formins, Arp2/3 complex, and Rho kinase. We also show that the physical adhesion of cells to galectin-8 is stronger than the adhesion to fibronectin. Notably, galectin-8 and fibronectin differentially regulate cell spreading and focal adhesion formation, yet they act synergistically to upregulate the number and length of filopodia. The physiological significance of the coherent cellular response to a molecularly complex matrix is discussed.

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confidence: 75%

Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates

Sancho

Chung

et al. 2021

Journal of Cell Science

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“…Most studies evaluating the effect of galectins on cytokine and chemokine production have focused on individual members of the galectin family and their effect on specific cell types. Recent studies have shown that galectin-3 and galectin-8 can promote the expression of CXCL10 in human fibroblasts and mouse osteoblasts, respectively [ 21 , 22 ]. Our experiments indicate that, in addition to these galectins, chimeric galectin-1 also induces expression of CXCL10 in human fibroblasts of corneal origin independently of IFN-γ ( Figure 1 B).…”

Section: Resultsmentioning

confidence: 99%

Induction of CXCL10-Mediated Cell Migration by Different Types of Galectins

AbuSamra

Panjwani

Argüeso

2021

Cells

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Chemokines are an extended group of chemoattractant cytokines responsible for the recruitment of leukocytes into tissues. Among them, interferon-γ-inducible protein 10 (CXCL10) is abundantly expressed following inflammatory stimuli and participates in the trafficking of monocytes and activated T cells into sites of injury. Here, we report that different members of the galectin family of carbohydrate-binding proteins promote the expression and synthesis of CXCL10 independently of interferon-γ. Interestingly, CXCL10 induction was observed when galectins came in contact with stromal fibroblasts isolated from human cornea but not other cell types such as epithelial, monocytic or endothelial cells. Induction of CXCL10 by the tandem repeat galectin-8 was primarily associated with the chemotactic migration of THP-1 monocytic cells, whereas the prototype galectin-1 promoted the CXCL10-dependent migration of Jurkat T cells. These results highlight the potential importance of the galectin signature in dictating the recruitment of specific leukocyte populations into precise tissue locations.

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“…Indeed, even a cursory review of published literature reveals many examples of preclinical cancer models where primary tumor growth and/or the degree of metastasis are significantly reduced following administration of syngeneic cancer cell lines into immunocompetent hosts that are genetic knockouts for a range of genes/proteins. [84][85][86][87][88][89][90][91][92][93] These include many studies with known mismatches in gene expression between the cancer cells and the recipient knockout mice, 85,[87][88][89][90]92 where immune rejection of the allografts could be contributing to the significant reductions in tumor growth observed. Some of the results of Shiuan, et al, 90 investigating the effects of host EphrinA1-deficiency on breast cancer progression bear a striking similarity to our own observations concerning Samsn1 and myeloma.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the role of Samsn1 loss in multiple myeloma development

et al. 2020

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The protein SAMSN1 was recently identified as a putative tumor suppressor in multiple myeloma, with re‐expression of Samsn1 in the 5TGM1/KaLwRij murine model of myeloma leading to a near complete abrogation of intramedullary tumor growth. Here, we sought to clarify the mechanism underlying this finding. Intratibial administration of 5TGM1 myeloma cells into KaLwRij mice revealed that Samsn1 had no effect on primary tumor growth, but that its expression significantly inhibited the metastasis of these primary tumors. Notably, neither in vitro nor in vivo migration was affected by Samsn1 expression. Both knocking‐out SAMSN1 in the RPMI‐8226 and JJN3 human myeloma cell lines, and retrovirally expressing SAMSN1 in the LP‐1 and OPM2 human myeloma cell lines had no effect on either cell proliferation or migration in vitro. Altering SAMSN1 expression in these human myeloma cells did not affect the capacity of the cells to establish either primary or metastatic intramedullary tumors when administered intratibially into immune deficient NSG mice. Unexpectedly, the tumor suppressive and anti‐metastatic activity of Samsn1 in 5TGM1 cells were not evidenced following cell administration either intratibially or intravenously to NSG mice. Crucially, the growth of Samsn1‐expressing 5TGM1 cells was limited in C57BL/6/Samsn1−/− mice but not in C57BL/6 Samsn1+/+ mice. We conclude that the reported potent in vivo tumor suppressor activity of Samsn1 can be attributed, in large part, to graft‐rejection from Samsn1−/− recipient mice. This has broad implications for the design and interpretation of experiments that utilize cancer cells and knockout mice that are mismatched for expression of specific proteins.

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The Animal Lectin Galectin-8 Promotes Cytokine Expression and Metastatic Tumor Growth in Mice

Cited by 24 publications

References 62 publications

Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates

Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates

Induction of CXCL10-Mediated Cell Migration by Different Types of Galectins

Characterization of the role of Samsn1 loss in multiple myeloma development

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