Binding of a Sialic Acid-recognizing Lectin Siglec-9 Modulates Adhesion Dynamics of Cancer Cells via Calpain-mediated Protein Degradation

Background: Engagement of inhibitory CD33-related Siglecs on immune cells has been shown to influence interactions with cancer cells, including tumor immune evasion. Results:LGALS3BP binds with high affinity to CD33-related Siglecs and inhibits neutrophil activation. Conclusion: We identify LGALS3BP as novel, cancer-associated Siglec ligand that can influence neutrophil activation. Significance: The engagement of inhibitory CD33-related Siglecs by LGALS3BP could support immune evasion of tumor cells.

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“…1A). This result is in accordance with other studies that identified mucins as Siglec-9 ligands (33,34).…”

Section: Identification Of Lgals3bp As a Sialic Acid-dependentsupporting

confidence: 83%

“…Several groups have identified other cancer cell-associated ligands for CD33rSiglecs, including mucins such as MUC-1 and MUC-16 (33,34,34,(41)(42)(43)(44). We also confirmed that tumor cell-associated mucins bind to Siglec-9 by using O-sialoglycoprotein-endopeptidase (Fig.…”

Section: Discussionmentioning

confidence: 99%

Lectin Galactoside-binding Soluble 3 Binding Protein (LGALS3BP) Is a Tumor-associated Immunomodulatory Ligand for CD33-related Siglecs

Läubli

Alisson-Silva

Stanczak

et al. 2014

Journal of Biological Chemistry

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“…Other recent analysis of Siglec-9 in cancer focused on activation of tumor cells via Siglec-9 ligands, such as mucin 1 (41,42). Previous analysis also identified Siglec-7 and -9 ligands present in colorectal cancer and also found a role for those Siglecs in the generation of tumor-associated macrophages (43).…”

Section: Discussionmentioning

confidence: 98%

Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer

Läubli¹,

Pearce²,

Schwarz³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

202

244

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Certain pathogenic bacteria are known to modulate the innate immune response by decorating themselves with sialic acids, which can engage the myelomonocytic lineage inhibitory receptor Siglec-9, thereby evading immunosurveillance. We hypothesized that the well-known up-regulation of sialoglycoconjugates by tumors might similarly modulate interactions with innate immune cells. Supporting this hypothesis, Siglec-9-expressing myelomonocytic cells found in human tumor samples were accompanied by a strong up-regulation of Siglec-9 ligands. Blockade of Siglec-9 enhanced neutrophil activity against tumor cells in vitro. To investigate the function of inhibitory myelomonocytic Siglecs in vivo we studied mouse Siglec-E, the murine functional equivalent of Siglec-9. Siglec-E-deficient mice showed increased in vivo killing of tumor cells, and this effect was reversed by transgenic Siglec-9 expression in myelomonocytic cells. Siglec-Edeficient mice also showed enhanced immunosurveillance of autologous tumors. However, once tumors were established, they grew faster in Siglec-E-deficient mice. In keeping with this, Siglec-E-deficient macrophages showed a propensity toward a tumor-promoting M2 polarization, indicating a secondary role of CD33-related Siglecs in limiting cancer-promoting inflammation and tumor growth. Thus, we define a previously unidentified impact of inhibitory myelomonocytic Siglecs in cancer biology, with distinct roles that reflect the dual function of myelomonocytic cells in cancer progression. In keeping with this, a human polymorphism that reduced Siglec-9 binding to carcinomas was associated with improved early survival in nonsmall-cell lung cancer patients, which suggests that Siglec-9 might be therapeutically targeted within the right time frame and stage of disease.hypersialylation | tumor-associated macrophages | tumor-associated neutrophils | immune evasion | tumor-associated inflammation

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“…These results suggested that the HCC with multiple observed lesions had more serious problems in protein degradation disorder. Although, the disturbance of protein degradation has been reported to be closely associated with different cancer types [40][41][42][43], the underlying mechanisms of the disturbance of UBC signaling pathway, which only occurred in HCC with multiple observed lesions, are not clear and need further investigation. On the other hand, the ERK signaling pathway is only enriched in the HCC with a single lesion, but it is normally regulated in HCC with multiple lesions; ERK signals were well known as an extremely important regulator of cell growth and proliferation.…”

Section: Ipa Network Analysis Of the Differentially Expressed Proteinsmentioning

confidence: 92%

Comparative analysis of primary hepatocellular carcinoma with single and multiple lesions by iTRAQ-based quantitative proteomics

Xing

Huang

Wang

et al. 2015

Journal of Proteomics

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Binding of a Sialic Acid-recognizing Lectin Siglec-9 Modulates Adhesion Dynamics of Cancer Cells via Calpain-mediated Protein Degradation

Cited by 19 publications

References 22 publications

Lectin Galactoside-binding Soluble 3 Binding Protein (LGALS3BP) Is a Tumor-associated Immunomodulatory Ligand for CD33-related Siglecs

Lectin Galactoside-binding Soluble 3 Binding Protein (LGALS3BP) Is a Tumor-associated Immunomodulatory Ligand for CD33-related Siglecs

Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer

Comparative analysis of primary hepatocellular carcinoma with single and multiple lesions by iTRAQ-based quantitative proteomics

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