Galectins as modulators of tumor progression in head and neck squamous cell carcinomas

Saussez, Sven; Camby, Isabelle; Toubeau, Gérard; Kiss, Róbert

doi:10.1002/hed.20559

Cited by 49 publications

(51 citation statements)

References 93 publications

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“…The role of Gal-1 in angiogenesis seems to be tissue-specific as Gal-1 expression correlates with endothelial cell markers in advanced prostate cancer but not in human breast cancer. These findings are consistent with the ability of Gal-1 to induce angiogenesis in oligodendroglioma (30), B16 melanoma (31), and Kaposi's sarcoma (26) but not in other tumor types such as Lewis lung carcinoma (41).…”

Section: Discussionsupporting

confidence: 83%

“…Given the pleiotropic functions of Gal-1 in the tumor microenvironment, including its role in angiogenesis (26,31,39,40), cell adhesion and invasiveness (16,30), and immunosuppression (23)(24)(25)41), upregulation of Gal-1 may dramatically influence prostate cancer progression. In this regard, Gal-1 is expressed in endothelial cells (42)(43)(44) and is upregulated in various cancer types (6).…”

Section: Discussionmentioning

confidence: 99%

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A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease

et al. 2013

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Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the "galectin signature" of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evolution, whereas expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during prostate cancer progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in prostate cancer angiogenesis. In human prostate cancer tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in prostate cancer cells reduced tumor vascularization without altering expression of other angiogenesis-related genes. Collectively, our findings identify a dynamically regulated "galectin-specific signature" that accompanies disease evolution in prostate cancer, and they highlight a major role for Gal-1 as a tractable target for antiangiogenic therapy in advanced stages of the disease. Cancer Res; 73(1); 86-96. Ó2012 AACR.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease

et al. 2013

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“…Each monomer is composed of a carbohydrate-recognition domain that recognizes a wide range of glycoproteins and glycolipids (13). Gal-1 expression in cancer-associated stroma is correlated with poor survival in several types of cancer including breast, prostate, and head and neck cancers (14)(15)(16)(17). We previously reported (18) that increased Gal-1 expression in cancer-associated stroma and the tumor-invasive front is significantly correlated with a poor prognosis in OSCC.…”

Section: Introductionmentioning

confidence: 99%

Targeting Galectin-1 in Carcinoma-Associated Fibroblasts Inhibits Oral Squamous Cell Carcinoma Metastasis by Downregulating MCP-1/CCL2 Expression

Hong

et al. 2011

Clinical Cancer Research

126

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Purpose: Carcinoma-associated fibroblasts (CAFs) in tumor stroma play an important role in tumor progression and have been associated with a poor prognosis in oral squamous cell carcinoma (OSCC). However, how CAFs influence OSCC malignancy and whether normalizing CAFs inhibits cancer progression remain unclear.Experimental Design: The relationship between the expression of Galectin-1 (Gal-1) and alpha-smooth muscle actin (a-SMA, a CAF marker) in OSCC patient samples and primary cultured CAFs was examined by quantitative real-time PCR, Western blotting, and immunofluorescence. To examine the effect of Gal-1 on CAF activation and CAF-mediated tumor invasion and migration in vitro, Gal-1 expression was knocked down by small hairpin RNA. Finally, cancer cells and CAFs were coimplanted into SCID mice to evaluate the effect of Gal-1 on CAF-modulated tumor progression in vivo.Results: Gal-1 expression is positively associated with a-SMA in the stroma of OSCC specimens. Gal-1 knockdown decreases activated CAF characteristics, resulting in a decrease in a-SMA expression and extracellular matrix protein production. Notably, blocking Gal-1 expression significantly inhibits CAFconditioned medium-induced tumor cell migration and invasion, possibly by reducing the production of monocyte chemotactic protein-1 (MCP-1/CCL2). MCP-1 induces the migration of OSCC cells by binding to the receptor CCR2; adding an MCP-1 antibody to CAF-conditioned medium that inhibits the interaction between MCP-1 and CCR2 abolishes migration. Finally, we found that Gal-1 knockdown in CAFs significantly reduces CAF-augmented tumor growth and metastasis in vivo.Conclusions: Our findings demonstrate that Gal-1 regulates CAF activation and indicate that targeting Gal-1 in CAFs inhibits OSCC metastasis by modulating MCP-1 expression.

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“…Our study identified the involvement of galectin-3 (Gal-3), a member of the β-gal-binding galectin family of proteins, in BMME-mediated cell proliferation, protection, and BM lodgment. Gal-3 associates with cell proliferation, migration, adhesion, and apoptosis (22)(23)(24)(25)(26), and moreover is associated with disease progression, metastasis, and drug resistance in various cancers (27)(28)(29)(30)(31), but the role of Gal-3 in leukemia has remained largely unknown.…”

mentioning

confidence: 99%

Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia

Yamamoto-Sugitani

Kuroda

Ashihara

et al. 2011

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

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Bone marrow (BM) microenvironment (BMME) constitutes the sanctuary for leukemic cells. In this study, we investigated the molecular mechanisms for BMME-mediated drug resistance and BM lodgment in chronic myelogenous leukemia (CML). Gene-expression profile as well as signal pathway and protein analyses revealed that galectin-3 (Gal-3), a member of the β-gal–binding galectin family of proteins, was specifically induced by coculture with HS-5 cells, a BM stroma cell-derived cell line, in all five CML cell lines examined. It was also found that primary CML cells expressed high levels of Gal-3 in BM. Enforced expression of Gal-3 activated Akt and Erk, induced accumulation of Mcl-1, and promoted in vitro cell proliferation, multidrug resistance to tyrosine kinase inhibitors for Bcr-Abl and genotoxic agents as a result of impaired apoptosis induction, and chemotactic cell migration to HS-5–derived soluble factors in CML cell lines independently of Bcr-Abl tyrosine kinase. The conditioned medium from Gal-3–overexpressing CML cells promoted in vitro cell proliferation of CML cells and HS-5 cells more than did the conditioned medium from parental cells. Moreover, the in vivo study in a mice transplantation model showed that Gal-3 overexpression promoted the long-term BM lodgment of CML cells. These results demonstrate that leukemia microenvironment-specific Gal-3 expression supports molecular signaling pathways for disease maintenance in BM and resistance to therapy in CML. They also suggest that Gal-3 may be a candidate therapeutic target to help overcome BMME-mediated therapeutic resistance.

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Galectins as modulators of tumor progression in head and neck squamous cell carcinomas

Cited by 49 publications

References 93 publications

A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease

A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease

Targeting Galectin-1 in Carcinoma-Associated Fibroblasts Inhibits Oral Squamous Cell Carcinoma Metastasis by Downregulating MCP-1/CCL2 Expression

Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia

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