CXCR4-mediated adhesion and MMP-9 secretion in head and neck squamous cell carcinoma

Samara, Ghassan; Lawrence, Diana M.; Chiarelli, Christian; Valentino, Michael D.; Lyubsky, Sergey; Zucker, Stanley; Vaday, Gayle G.

doi:10.1016/j.canlet.2004.04.035

Cited by 92 publications

(57 citation statements)

References 27 publications

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“…5A). These data are inline with previously published reports showing the CXCL12/CXCR4 -mediated expression of MMP-9 in cancer cells (2,(36)(37)(38)(39)(40). Furthermore, these data suggest that CXCL12/CXCR4 transactivation of HER2 is an upstream event of Akt activation in prostate cancer cells.…”

Section: Discussionsupporting

confidence: 92%

CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone

Chinni

Yamamoto

Dong

et al. 2008

Molecular Cancer Research

119

102

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Chemokines and their receptors function in migration and homing of cells to target tissues. Recent evidence suggests that cancer cells use a chemokine receptor axis for metastasis formation at secondary sites. Previously, we showed that binding of the chemokine CXCL12 to its receptor CXCR4 mediated signaling events resulting in matrix metalloproteinase-9 expression in prostate cancer bone metastasis. A variety of methods, including lipid raft isolation, stable overexpression of CXCR4, cellular adhesion, invasion assays, and the severe combined immunodeficient -human bone tumor growth model were used. We found that (a) CXCR4 and HER2 coexist in lipid rafts of prostate cancer cells; (b) the CXCL12/CXCR4 axis results in transactivation of the HER2 receptor in lipid rafts of prostate cancer cells; (c) Src kinase mediates CXCL12/CXCR4 transactivation of HER2 in prostate cancer cells; (d) a pan-HER inhibitor desensitizes CXCR4-induced transactivation and subsequent matrix metalloproteinase-9 secretion and invasion; (e) lipid raft -disrupting agents inhibited raft-associated CXCL12/CXCR4 transactivation of the HER2 and cellular invasion; (f) overexpression of CXCR4 in prostate cancer cells leads to increased HER2 phosphorylation and migratory properties of prostate cancer cells; and (g) CXCR4 overexpression enhances bone tumor growth and osteolysis. These data suggest that lipid rafts on the cell membrane are the key site for CXCL12/CXCR4 -induced HER2 receptor transactivation. This transactivation contributes to enhanced invasive signals and metastatic growth in the bone microenvironment.

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Section: Discussionsupporting

confidence: 92%

CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone

Chinni

Yamamoto

Dong

et al. 2008

Molecular Cancer Research

119

102

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“…Knockdown of Akt using siRNA also abrogated FNinduced MMP-9 expression (not shown). Head and neck squamous cell carcinoma adhesion to FN and induction of MMP-9 secretion were increased by the chemokine CXCCL12, whereas the addition of an inhibitor of ERK-1/2 signaling, PD98059, reduced the effects of CXCL12 (42). Also, treatment of cells with ERK inhibitors, U0126 and PD98059, and PI3K inhibitors, wortmannin and LY294002, dramatically suppressed the secretion of MMP-9 induced by FN.…”

Section: Discussionmentioning

confidence: 98%

Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells

Han

Ritzenthaler

Sitaraman

et al. 2006

Journal of Biological Chemistry

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Matrix metalloproteinases (MMPs) 2 are a family of zinc enzymes responsible for degradation of extracellular matrix components including basement membrane collagen, interstitial collagens, fibronectin (FN), and various proteoglycans during normal remodeling and repair processes (1, 2). The potent proteolytic activities of MMPs are mainly regulated by the concomitant expression of specific tissue inhibitors of matrix metalloproteinases (3). Excessive or inappropriate expression of MMPs may contribute to the pathogenesis of tissue destructive processes in a wide variety of diseases including lung disorders like bronchial asthma, chronic obstructive pulmonary disease, acute lung injury, pulmonary hypertension, and interstitial lung diseases (2, 4). In addition, MMPs have been implicated in the progression and metastases of different tumors including lung cancer (see later in text).One member of the MMP family is the 92-kDa type IV collagenase MMP-9. The MMP-9 gene is encoded on chromosome 20 and its expression is under the control of a 2.2-kb upstream regulatory sequence harboring binding sites for AP-1, NF-B, Sp1, and others (5). MMP-9 expression is increased in malignant cancers when compared with benign tumors and non-invasive ones, and there is compelling in vitro and in vivo evidence for a role of MMP-9 in tumor invasion and angiogenesis (6, 7). Its dramatic overexpression in cancer and various inflammatory conditions suggest that this protease is a potential target for the development of novel therapeutic interventions (8).Because of its perceived importance, our research focuses on the factors that increase MMP-9 expression in the lung. Our search led us to FN, a matrix glycoprotein highly expressed in tobacco-related lung disease that has been shown to stimulate lung carcinoma cell growth through several mechanisms (9 -11). Cell adhesion to FN results in MMP secretion in normal and tumor cell systems (12)(13)(14). These studies suggest that tumor cell interactions with FN might lead to MMP-9 expression thereby promoting cancer cell migration, invasion, and related processes. However, the mechanisms by which FN stim-* This work was supported by American Lung Association Bioresearch Grant RG-10215N (to S. W. H.) and by a Merit Review Grant from the Department of Veterans Affairs (to J. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.

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“…Recently, CXCR4 was further reported to participate in tumor metastasis to regional lymph nodes (26). In head and neck squamous cell carcinomas, CXCR4 has been suggested to act as a regulator of metastatic processes by increasing tumor cell adhesion and secretion of matrix metalloproteinase-9, which may enhance the detachment of highly motile tumor cells from the primary lesions (27). In human oral squamous cell carcinoma, CXCR4 has not been shown responsible for lung metastasis but was associated with the establishment of secondary tumor foci in regional lymph nodes (28,29).…”

Section: Discussionmentioning

confidence: 99%

The Expression of Functional Chemokine Receptor CXCR4 Is Associated with the Metastatic Potential of Human Nasopharyngeal Carcinoma

Deng

Bian

et al. 2005

Clinical Cancer Research

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Purpose: Chemokine receptors are implicated in metastasis of several malignant tumors. This study was done to evaluate the contribution of chemokine receptors CXCR4 and CCR7 to metastasis of human nasopharyngeal carcinoma. Experimental Design: Reverse transcription-PCR, immunohistochemistry, and flow cytometry were used to evaluate mRNA and protein expression of CXCR4 and CCR7 in nasopharyngeal carcinoma tumor tissues and cell lines. Chemotaxis assays were used to evaluate the function of CXCR4 in nasopharyngeal carcinoma cells. Antisense CXCR4 was used to inhibit receptor expression and to block metastasis of human nasopharyngeal carcinoma cells in vivo in athymic mice. Results: CXCR4 protein was detected in tumor cells in 31of 40 primary human nasopharyngeal carcinoma and in 13 of 15 lymph node metastases. CXCR4 transcripts were detected in eight CXCR4 protein^positive primary nasopharyngeal carcinoma tissues and seven nasopharyngeal carcinoma cell lines tested. On the other hand, the transcripts for CCR7 were detected only in four primary nasopharyngeal carcinoma tissues and in none of the nasopharyngeal carcinoma cell lines. In functional experiments, metastatic nasopharyngeal carcinoma cell lines that expressed high levels of CXCR4 were found to migrate in response to the CXCR4 ligand SDF-1a. Transfection of antisense CXCR4 in metastatic nasopharyngeal carcinoma cells inhibited the expression of CXCR4 and SDF-1a-induced cell migration in vitro and reduced the capacity of the tumor cells to form metastasis in the lungs and lymph nodes when injected in athymic mice. Conclusion:The expression of functional CXCR4 but not CCR7 is correlated with the metastatic potential of human nasopharyngeal carcinoma cells. Therefore, CXCR4 may be considered as a potential target for the prevention of nasopharyngeal carcinoma metastasis.

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CXCR4-mediated adhesion and MMP-9 secretion in head and neck squamous cell carcinoma

Cited by 92 publications

References 27 publications

CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone

CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone

Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells

The Expression of Functional Chemokine Receptor CXCR4 Is Associated with the Metastatic Potential of Human Nasopharyngeal Carcinoma

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