CXCR4 expression is associated with lymph-node metastasis of oral squamous cell carcinoma

Ishikawa, Tohru; Nakashiro, Koh‐ichi; Hará, Saburo; Kłosek, Sebastian; Li, Chunnan; Shintani, Satoru; Hamakawa, Hiroyuki

doi:10.3892/ijo.28.1.61

Cited by 52 publications

(74 citation statements)

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“…In this study, we show that CXCR4 silencing leads to a significant decrease of Tca8113 cells migration and invasion and provide evidence that CXCR4 regulates the transcriptional levels of MMP-9 and MMP-13 in Tca8113 cells. We The finding that CXCR4 silencing led to a significant decrease of Tca8113 cells migration and invasion was consistent with many previous reports, which showed that high levels of CXCR4 expression promoted OSCC cell invasion (26). Moreover, functional blocking of CXCR4 by TN14003 also led to decreased cell migration and invasion, which was also consistent with reports that TN14003 treatment decreased migration of breast cancer cells and pancreatic cancer cells in vitro and reduced pulmonary metastasis of breast cancer in SCID mice (30,39).…”

Section: Discussionsupporting

confidence: 81%

“…Expression of MMPs and other extracellular proteinases have been shown to positively correlate with the progression of cancer in patients (10,42). It is interesting to note that several studies have shown that the expression levels of CXCR4 were also highly upregulated in human head and neck squamous cell carcinoma and OSCC, suggesting that MMPs and CXCR4 expression levels are likely coupled (26,43,44). However, it is unknown how these genes regulate each other during tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

“…First, several MMPs, including MMP2, MMP-9, and MMP-13, directly or indirectly interact with CXCR4, which could alter MMP-mediated pericellular proteolysis (23)(24)(25). Second, several studies have shown that CXCR4, and MMP2, MMP-9, and MMP-13 were highly upregulated in human OSCC, suggesting that their expression levels are likely coupled (26,27). Herein, we present evidence that CXCR4 regulates tumor cell migration and invasion by altering the expression of MMP-9 and MMP-13.…”

Section: Introductionmentioning

confidence: 99%

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CXCR4 Promotes Oral Squamous Cell Carcinoma Migration and Invasion through Inducing Expression of MMP-9 and MMP-13 via the ERK Signaling Pathway

Helman

et al. 2011

Molecular Cancer Research

111

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The increased migration and invasion of oral squamous cell carcinoma cells are key events in the development of metastasis to the lymph nodes and distant organs. Although the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor-1a, have been found to play an important role in tumor invasion, its precise role and potential underlying mechanisms remain largely unknown. In this study, we showed that knockdown of CXCR4 significantly decreased Tca8113 cells migration and invasion, accompanied with the reduction of MMP-9 and MMP-13 expression. Inhibition of ligand binding to CXCR4 by a specific antagonist TN14003, also led to reduced cancer cell migration and invasion. Because the degradation of the extracellular matrix and the basement membrane by proteases, such as matrix metalloproteinases (MMP) is critical for migration and invasion of cancer cells, we investigated the expression of several MMPs and found that the expression of functional MMP-9 and MMP-13 was selectively decreased in CXCR4 knockdown cells. More importantly, decreased cell migration and invasion of CXCR4 knockdown cells were completely rescued by exogenous expression of MMP-9 or MMP-13, indicating that the two MMPs are downstream targets of CXCR4-mediated signaling. Furthermore, we found the level of phosphorylated extracellular signal-regulated kinase (ERK) was significantly decreased in CXCR4-silenced cells, suggesting that ERK may be a potential mediator of CXCR4-regulated MMP-9 and MMP-13 expression in Tca8113 cells. Taken together, our results strongly suggest the underlying mechanism of CXCR4 promoting Tca8113 migration and invasion by regulating MMP-9 and MMP-13 expression perhaps via activation of the ERK signaling pathway. Mol Cancer Res; 9(2); 161-72. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CXCR4 Promotes Oral Squamous Cell Carcinoma Migration and Invasion through Inducing Expression of MMP-9 and MMP-13 via the ERK Signaling Pathway

Helman

et al. 2011

Molecular Cancer Research

111

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“…Tissues to which tumor cells selectively metastasize, such as the lymph nodes, bone, lungs, and liver, are often the most abundant source of SDF-1α (Muller et al, 2001). A significant association between CXCR4 expression and lymph node metastasis has been reported in OSCC Uchida et al, 2004;Ishikawa et al, 2006). However, the molecular mechanisms associated with CXCR4-mediated OSCC metastasis remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

CXCL12/SDF‐1α Activates NF‐κB and Promotes Oral Cancer Invasion through the Carma3/Bcl10/Malt1 Complex

Rehman

Wang

2009

Int J Oral Sci

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“…Chemokines have previously been reported to play an important role in both tumor growth and in establishing organ-specific metastases in several malignancies (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The expression of CXCR4 in gastric cancer correlates with peritoneal dissemination (9) and cancerous CXCL12 expression was an independent prognostic factor in gastric cancer (10) and the expression of CCR6 in colorectal cancer is associated with synchronous liver metastases (11).…”

Section: Introductionmentioning

confidence: 99%

High CCR7 mRNA expression of cancer cells is associated with lymph node involvement in patients with esophageal squamous cell carcinoma

Iwahashi¹

2009

Int J Oncol

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Abstract. Esophageal squamous cell carcinoma (SCC) is one of the biological malignant tumors. Once a tumor invades the submucosa, an incidence of lymph node (LN) metastases is very high, thus resulting in poor survival. Recently, chemokines have been reported to play an important role in organspecific metastases in several malignancies. In particular, CCR7 has been reported to be associated with LN metastases by immunohistochemistry. However, there have been no studies of quantitative analyses of CCR7 mRNA expression on cancer cells. In this study, we investigated the clinical significance of the expression of CCR7 in the establishment of LN metastases of esophageal SCC. A series of 78 patients with esophageal SCC who underwent esophagectomy were consecutively selected. The expression of CCR7 mRNA from tumor tissue samples was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), and that from cancer cell samples collected using laser microdissection system was analyzed by qRT-PCR. Immunohistochemical staining of CCR7 was also performed. Although CCR7 mRNA expression in tumor tissues demonstrated no association with the LN metastases, that in cancer cells correlated with LN metastases (p<0.05) due to the fact that not only cancer cells but also infiltrating lymphocytes expressed CCR7 in tumor tissue. Multivariate logistic regression analysis revealed a high CCR7 expression in cancer cells to be an independent predictive factor for LN metastases. These results suggested that CCR7 expression might play an important role in establishing LN metastases in patients with esophageal SCC.

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CXCR4 expression is associated with lymph-node metastasis of oral squamous cell carcinoma

Cited by 52 publications

References 0 publications

CXCR4 Promotes Oral Squamous Cell Carcinoma Migration and Invasion through Inducing Expression of MMP-9 and MMP-13 via the ERK Signaling Pathway

CXCR4 Promotes Oral Squamous Cell Carcinoma Migration and Invasion through Inducing Expression of MMP-9 and MMP-13 via the ERK Signaling Pathway

CXCL12/SDF‐1α Activates NF‐κB and Promotes Oral Cancer Invasion through the Carma3/Bcl10/Malt1 Complex

High CCR7 mRNA expression of cancer cells is associated with lymph node involvement in patients with esophageal squamous cell carcinoma

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