Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment

Ito, Koichi; Stannard, Kimberley; Gabutero, Elwyn; Clark, Amanda M.; Neo, Shiyong; Onturk, Selda; Blanchard, Helen; Ralph, Stephen John

doi:10.1007/s10555-012-9388-2

Cited by 105 publications

(89 citation statements)

References 173 publications

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“…11 Furthermore, gal-1 blunts T cell responses via promoting accumulation and expansion of Tregs. 12 It is overexpressed by numerous malignant cell types, including ovarian cancer, by activated vascular endothelial cells, by normal activated T cells and by Treg. In anti-VEGF refractory tumors, gal-1 has been documented to bind VEGF receptor 2 and to maintain angiogenesis.…”

Section: Vegfmentioning

confidence: 99%

Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course

et al. 2015

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Neoplastic cells can escape immune control leading to cancer growth. Regulatory T cells (Treg), myeloidderived suppressor cells (MDSC) and tumor-associated macrophages (TAM) are crucial in immune escape. TAM are divided based on their immune profile, M1 are immunostimulatory while M2 are immunosuppressive. Research so far has mainly focused on the intratumoral behavior of these cells. This study, on the other hand, explored the systemic changes of the key metabolites [IL-4 (interleukin), IL-13, arginase, IL-10, VEGF-A (vascular endothelial growth factor), CCL-2 (chemokine (C-C) motif ligand 2) and TGF-b (transforming growth factor)] linked to Treg, MDSC and TAM during the course of the disease in ovarian and fallopian tube cancer patients. Serum samples were therefore analyzed at diagnosis, after (interval)-debulking surgery and after chemotherapy (paclitaxel-carboplatin). We also determined galectin-1 (gal-1), involved in angiogenesis and tumor-mediated immune evasion. We found significantly lower levels of IL-10, VEGF-A, TGF-b and arginase and higher levels of gal-1 after chemotherapy compared to diagnosis. After debulking surgery, a decrease in IL-10 was significant. Gal-1 and CCL-2 appeared independent prognostic factors for progression-free and overall survival (OS) (multivariate analysis). These results will help us in the decision making of future therapies in order to further modulate the immune system in a positive way.

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Section: Vegfmentioning

confidence: 99%

Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course

et al. 2015

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“…These components not only promote tumor progression and metastasis, but also induce immunosuppression and protect tumor cells from host immune attack (2). As a major barrier to cancer progression, the immune system controls tumor elimination; however, it is modulated by factors in the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Targeting Blockage of STAT3 in Hepatocellular Carcinoma Cells Augments NK Cell Functions via Reverse Hepatocellular Carcinoma–Induced Immune Suppression

Sun

Sui

Zhang

et al. 2013

Molecular Cancer Therapeutics

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STAT3 is an important transcriptional factor for cell growth, differentiation, and apoptosis. Although evidence suggests a positive role for STAT3 in cancer, the inhibitory effects of tumor STAT3 on natural killer (NK) cell functions in human hepatocellular carcinoma are unclear. In this study, we found that blocking STAT3 in hepatocellular carcinoma cells enhanced NK-cell antitumor function. In the case of STAT3-blocked hepatocellular carcinoma cells, NKG2D ligands were upregulated, which promoted recognition by NK cells. Importantly, the cytokine profile of hepatocellular carcinoma cells was altered; in particular, TGF-b and interleukin 10 (IL-10) expression was reduced, and type I interferon (IFN) was induced, thus facilitating NK-cell activation. Indeed, the cytotoxicity of NK cells treated with supernatant from STAT3-blocked hepatocellular carcinoma cells was augmented, with a concomitant elevation of molecules associated with NK cytolysis. Further experiments confirmed that the recovery of NK cells depended on the downregulation of TGF-b and upregulation of type I IFN derived from STAT3-blocked hepatocellular carcinoma cells. These findings demonstrated a pivotal role for STAT3 in hepatocellular carcinoma-mediated NK-cell dysfunction, and highlighted the importance of STAT3 blockade for hepatocellular carcinoma immunotherapy, which could restore NK-cell cytotoxicity in addition to its direct influence on tumor cells.

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“…However, some reports show GAL1 inhibits the viability, proliferation and Th1 cytokine production of non-malignant T cells in patients with leukemic cutaneous T-cell lymphoma (19), and GAL1 silencing imparts colorectal cancer with the ability to proliferate and escape apoptosis (20). Further research suggests that GAL1 plays vital pro-tumorigenic roles within the tumor microenvironment (21), and stimulates the proliferation of melanoma and neo-angiogenesis processes (22). In the present study, knockdown of GAL1 inhibited the independent growth and invasive potential, and induced apoptosis in OS cells in vitro and in vivo, suggesting that GAL1 may represent a promising and effective target for antitumor therapy.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of galectin-1 suppresses the growth and invasion of osteosarcoma cells through inhibition of the MAPK/ERK pathway

et al. 2014

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Abstract. Galectin-1 (GAL1), a widely expressed β-galactoside-binding protein, exerts pleiotropic biological functions. GAL1 has been found to be upregulated in many malignancies; yet the role of GAL1 in the pathophysiology of human osteosarcoma (OS) remains uncertain. The present study was carried out to investigate the expression of GAL1 in human OS tissues and to explore its effects on the growth and invasion of OS cells. OS and corresponding adjacent non-cancerous tissues (ANCT) were collected from 30 consecutive cases. The expression of GAL1 was detected by immunohistochemical assay through tissue microarray procedure. Using small hairpin RNA (shRNA)-mediated GAL1 knockdown (Lv-shGAL1) in OS (MG-63 and U-2 OS) cells, we observed the changes in the malignant phenotype in OS cells in vitro and in vivo. As a consequence, the positive expression of GAL1 was significantly higher in OS tissues than that in the ANCT (63.3 vs. 36.7%, P=0.029), and was positively correlated with distant metastasis in the OS patients (P=0.022). Knockdown of GAL1 suppressed cell proliferative activities and invasive potential and induced apoptosis in OS cells with decreased expression of p38MAPK, p-ERK, Ki-67 and matrix metallopeptidase-9 (MMP-9) and increased expression of caspase-3. In addition, the tumor volume in the MG-63 subcutaneous tumor models treated with Lv-shGAL1 was significantly smaller than that in the negative control (NC) group (P<0.01). Altogether, our findings indicate that high expression of GAL1 is associated with distant metastasis of OS patients, and knockdown of GAL1 inhibits growth and invasion of OS cells possibly through inhibition of the MAPK/ERK pathway, suggesting that GAL1 may represent a potential target for the treatment of cancer.

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Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment

Cited by 105 publications

References 173 publications

Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course

Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course

Targeting Blockage of STAT3 in Hepatocellular Carcinoma Cells Augments NK Cell Functions via Reverse Hepatocellular Carcinoma–Induced Immune Suppression

Knockdown of galectin-1 suppresses the growth and invasion of osteosarcoma cells through inhibition of the MAPK/ERK pathway

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