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

Wu, Meng-Hsiu; Hong, Hsiao Chin; Hong, Tse-Ming; Chiang, Wei Fan; Jin, Ying; Chen, Yuh Ling

doi:10.1158/1078-0432.ccr-10-1824

Cited by 124 publications

(109 citation statements)

References 42 publications

(48 reference statements)

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“…29 Recent findings indicate that Gal-1 in cancer-associated fibroblasts can promote the metastasis of oral squamous cell carcinoma by modulating monocyte chemotactic protein-1 (MCP-1/CCL2). 30 The present study demonstrates for the first time that Gal-1 contributes to kidney cancer progression via activation of CXCR4, which is the most common chemokine receptor overexpressed in human cancers. Interaction of CXCR4 with its sole ligand CXCL12 (also called stromal-derived factor1a) is reportedly involved in the regulation of chemotaxis, invasion, and organ-specific metastases.…”

Section: Discussionmentioning

confidence: 56%

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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Galectin-1, a b-galactoside-binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1-silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-kB (NF-kB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-kB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease. 25: 148625: -149525: , 201425: . doi: 10.1681 Renal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies. 1 More than one third of patients will present with locally advanced or metastatic disease at the time of diagnosis. 2 The 5-year survival rate of metastatic RCC is only 10% because of resistance to chemotherapy and radiation therapy. 3 Although cytokine therapy with IFN-a and IL-2 is the gold standard treatment, its overall efficacy rate is limited by its significant toxicity. 4 Recently, several molecular targeting drugs, including sunitinib and temsirolimus, have been approved for advanced RCC. 4 However, treatment response is not long-standing and overall survival remains poor. Thus, the identification of novel molecular targets in RCC is urgently needed for the development of effective therapies. J Am Soc Nephrol

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Section: Discussionmentioning

confidence: 56%

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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“…[238][239][240][241][242][243][244][245][246][247] Treatments that can enhance the ability of fibroblasts to stimulate tumor cell invasion include irradiation 182 and reactive oxygen species, 183,248,249 as well as lifestyle-correlated factors, such as cigarette smoke 250 and areca nut extract. 251 Fibroblasts have been shown to stimulate tumor cell invasion through secretion of a number of factors, including chemokine (C-C motif) ligand 2 (CCL2), 183,252 260 and hepatocyte growth factor (HGF).…”

Section: Tumor Microenvironment and Invasionmentioning

confidence: 99%

“…183 Galectin production by tumor cells can also stimulate CCL2 production from fibroblasts. 252 Interleukin 1 from OSCC stimulates CCL7, HGF, and TGFb production by fibroblasts, 73 Other features of the tumor microenvironment have also been identified as stimulating HNSCC invasion, although not as thoroughly as cancer-associated fibroblasts. The perivascular niche has been associated with cancer stem cells and invasion.…”

Section: Tumor Microenvironment and Invasionmentioning

confidence: 99%

Mechanisms of Invasion in Head and Neck Cancer

Jimenez¹,

Jayakar²,

Ow³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-The highly invasive properties demonstrated by head and neck squamous cell carcinoma (HNSCC) are often associated with locoregional recurrence and lymph node metastasis in patients and is a key factor leading to an expected 5-year survival rate of approximately 50% for patients with advanced disease. It is important to understand the features and mediators of HNSCC invasion so that new treatment approaches can be developed.Objectives.-To provide an overview of the characteristics, mediators, and mechanisms of HNSCC invasion.Data Sources.-A literature review of peer-reviewed articles in PubMed on HNSCC invasion.Conclusions.-Histologic features of HNSCC tumors can help predict prognosis and influence clinical treatment decisions. Cell surface receptors, signaling pathways, proteases, invadopodia function, epithelial-mesenchymal transition, microRNAs, and tumor microenvironment are all involved in the regulation of the invasive behavior of HNSCC cells. Identifying effective HNSCC invasion inhibitors has the potential to improve outcomes for patients by reducing the rate of spread and increasing responsiveness to chemoradiation.

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“…GAL1 plays an important role in modulating HCC cell adhesion, polarization and in vivo tumor growth with critical implications in liver pathophysiology (9). Targeting GAL1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression (18). 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).…”

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

Cited by 124 publications

References 42 publications

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Mechanisms of Invasion in Head and Neck Cancer

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

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