Anoxia-Induced Up-Regulation of Interleukin-8 in Human Malignant Melanoma

Kunz, Manfred; Hartmann, Anke; Flory, Egbert; Toksoy, Atiye; Koczan, Dirk; Thiesen, Hans‐Jürgen; Mukaida, N; Neumann, Manfred; Rapp, Ulf R.; Bröcker, Eva‐Bettina; Gillitzer, R.

doi:10.1016/s0002-9440(10)65174-7

Cited by 87 publications

(75 citation statements)

References 48 publications

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“…Of interest is that some CXC chemokines such as IL-8/CXCL8 is presumed to be involved in neovascularization in some types of tumors through their potent angiogenic activities. 7,[22][23][24][25] Moreover, several lines of evidence indicate that chemokine receptors expressed on tumor cells may determine the destination of metastasis of several types of tumors such as breast cancer and melanoma. 26 -33 However, it remains elusive which chemokine receptor(s) is expressed by hepatoma.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] Persistent chronic infection with hepatitis B virus or hepatitis C virus frequently resulted in the development of hepatocellular carcinoma, which ranks as the eighth cause of death among human cancers and is endemic in Asia, Africa, and southern Europe. 9 We previously observed that the X protein of hepatitis B virus and the hepatitis C virus NS5A gene product can induce in vitro gene expression and protein production of interleukin (IL)-8/CXCL8, 10,11 one of CXC chemokines.…”

Section: Acjp) a Wide Variety Of Tumor Cells And Normal Cells Can Pmentioning

confidence: 99%

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Potential Interaction between CCR1 and Its Ligand, CCL3, Induced by Endogenously Produced Interleukin-1 in Human Hepatomas

Nakamoto

Nemoto-Sasaki

et al. 2003

The American Journal of Pathology

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Hepatoma cell lines can produce a massive amount of chemokines in response to various stimuli including hepatitis viruses and their products. However, it remains elusive on the types of chemokine receptor(s) expressed in the hepatoma tissues and its roles in hepatoma development. To clarify these points, we examined the chemokine receptor expression in six human hepatoma cell lines. All of the hepatoma cell lines constitutively and exclusively expressed CCR1 mRNA and its protein on their cell surface. CCR1 expression was also detected on hepatoma cells and to a lesser degree, on endothelial cells in hepatoma tissues but not in normal liver tissues. Furthermore, CCL3 expression was detected in hepatoma cells, endothelial cells, and to a lesser degree, fibroblast-like cells in hepatoma tissue, whereas only occasional vascular endothelial cells and inflammatory cells in normal liver tissues were weakly positive for CCL3. Moreover, the forskolin-mediated increases in intracellular cAMP concentrations were inhibited by the ligands for CCR1, CCL3, CCL4, and CCL5, suggesting that the expressed CCR1 was functional.

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Section: Discussionmentioning

confidence: 99%

Section: Acjp) a Wide Variety Of Tumor Cells And Normal Cells Can Pmentioning

confidence: 99%

Potential Interaction between CCR1 and Its Ligand, CCL3, Induced by Endogenously Produced Interleukin-1 in Human Hepatomas

Nakamoto

Nemoto-Sasaki

et al. 2003

The American Journal of Pathology

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“…The secretion of angiogenesis factors such as the fibroblast growth factor, VEGF, platelet-derived growth factor, interleukin-8, angiogenin, and CCN1, is enhanced in response to hypoxia (10,(14)(15)(16)(17)(18)(19)(20)(21)(22). The immediate early gene CCN1 (CYR61), a member of the CCN family, codes for a secreted heparin binding protein associated with the cell surface and extracellular matrix (23).…”

Section: Introductionmentioning

confidence: 99%

A Key Role for Cyclic AMP-Responsive Element Binding Protein in Hypoxia-Mediated Activation of the Angiogenesis Factor CCN1 (CYR61) in Tumor Cells

Meyuhas¹,

Pikarsky²,

Tavor³

et al. 2008

Molecular Cancer Research

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Hypoxia is a prominent feature of solid tumors known to contribute to malignant progression and therapeutic resistance. Cancer cells adapt to hypoxia using various pathways, allowing tumors to thrive in a low oxygen state. Induction of new blood vessel formation via the secretion of proangiogenic factors is one of the main adaptive responses engaged by tumor cells under hypoxic conditions. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays a pivotal role in mediating such responses. In addition, several other transcription factors have also been implicated in hypoxic gene regulation, either independently or in cooperation with HIF-1. In this work, we show that the expression of the angiogenesis-related, immediate early gene CCN1 (formerly known as CYR61), considered to be involved in tumor growth and invasiveness, is enhanced upon hypoxia stress primarily in a protein kinase A and cyclic AMP-responsive element binding protein (CREB) and CRE -dependent manner in various cell lines. The hypoxia-mediated activation of the CCN1 promoter is independent of HIF-1 and HIF-2, as shown by small interfering RNA knockdown. We identify the cis element in the mouse CCN1 promoter responsible for CREB binding to be one of two partial CRE sites present in the promoter. Moreover, we report for the first time that CREB-mediated CCN1 transcription is enhanced in hypoxic regions of tumors in vivo. Identifying and characterizing the molecular mechanisms that govern the response of tumors to hypoxia may be instrumental to identify the tumors that will respond favorably to inhibition of angiogenesis and thus lead to the development of treatments that could complement hypoxia-inducing treatment modalities.

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“…The increased expression of CXCL1 and CXCL2 (previously known as melanoma growth stimulatory activity alpha and beta, respectively) in melanoma lesions correlates with tumor progression. 10 The interaction between CXCL1 and the Il-8 receptor beta (CXCR2) is a major component required for serum-independent melanoma cell growth.11 The chemokine CXCL8 (previously known as IL-8) is a potent growth factor for melanoma cells 12,13 and also upregulates matrix metalloproteinase activity (MMP-2) in human melanoma cells. …”

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confidence: 99%

Clinical significance of CXCR3 and CXCR4 expression in primary melanoma

Longo-Imedio

Longo

Treviño

et al. 2005

Intl Journal of Cancer

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Tumor cell migration involved in metastases is a tightly regulated, nonrandom process. Chemokines have been identified as critical molecules guiding cell migration. We performed a prospective study to analyze a possible association between the expression of chemokine receptors CXCR3 and CXCR4 by primary melanoma and clinical outcome. Forty primary melanomas were available for analysis; 57% of the tumors expressed CXCR3 and 35% expressed CXCR4 by melanoma cells. At initial diagnosis, 5 patients had subclinical lymph node involvement and after a median follow-up time of 32 months, 2 additional patients developed regional lymph node metastases and 5 patients developed distant metastases. The expression of CXCR4, but not CXCR3, by melanoma cells in primary lesions was significantly associated with the presence of ulceration, increased tumor thickness, a greater risk of developing regional and distant metastases and a higher mortality rate. Our study underscores the value of CXCR4 expression as a useful marker for predicting outcome in patients with localized melanoma. In addition, our findings support that, among chemokine receptors, CXCR4 might be an appropriate therapeutic target for adjuvant therapy in patients at risk for metastatic disease. ' 2005 Wiley-Liss, Inc.Key words: melanoma; chemokine receptors; clinical significanceThe incidence of cutaneous melanoma has steeply increased in the last decade.1 The most important prognostic factors of the primary tumor include depth of invasion 2 and presence of ulceration.3,4 Roughly 20% of patients will develop metastases that are the main cause of death. The mechanisms involved in metastasis are not completely understood. The capability of a tumor clone to metastasize depends on its ability to disrupt the basal membrane, migrate, proliferate and survive to allow progressive growth at distant sites. The development of metastases implies a stepwise and organ-specific process. Tumor cell migration to target organs is achieved by a chemotactic response to certain molecules. Chemokines comprise a group of key molecules involved in migration of different cell lineages. They constitute a family of small proteins that are classified based on the specific cysteine motifs in their amino acid sequence. [5][6][7] Through their interaction with G-proteincoupled receptors, chemokines mediate many physiologic and pathologic processes involving cell migration. [5][6][7] Tumor cells might employ similar mechanisms to migrate to specific organs as do leukocytes and other cell types through the expression of certain chemokine receptors.8 Current evidence supports a strong role for chemokines in the complex process of metastasis.9 Moreover, chemokines have been identified as angiogenic factors that promote tumor cell growth and progression. The chemokines most thoroughly studied in melanoma are CXCL1, CXCL2 and CXCL8. The increased expression of CXCL1 and CXCL2 (previously known as melanoma growth stimulatory activity alpha and beta, respectively) in melanoma lesions correlates with tu...

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Anoxia-Induced Up-Regulation of Interleukin-8 in Human Malignant Melanoma

Cited by 87 publications

References 48 publications

Potential Interaction between CCR1 and Its Ligand, CCL3, Induced by Endogenously Produced Interleukin-1 in Human Hepatomas

Potential Interaction between CCR1 and Its Ligand, CCL3, Induced by Endogenously Produced Interleukin-1 in Human Hepatomas

A Key Role for Cyclic AMP-Responsive Element Binding Protein in Hypoxia-Mediated Activation of the Angiogenesis Factor CCN1 (CYR61) in Tumor Cells

Clinical significance of CXCR3 and CXCR4 expression in primary melanoma

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