Growth Regulated Oncogene-α expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC Receptor-2 dependent mechanism

Loukinova, Elena; Dong, Gang; Enamorado-Ayalya, Ileana; Thomas, Giovana R.; Chen, Zhong; Schreiber, Hans; Waes, Carter Van

doi:10.1038/sj.onc.1203687

Cited by 161 publications

(146 citation statements)

References 15 publications

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“…Differential roles of CXCR1 and CXCR2 in endothelial cell migration have been reported previously (Li et al, 2002. It was shown that the migration of CXCR1-and CXCR2-expressing endothelial cells is predominantly mediated through CXCR2 (Addison et al, 2000;Loukinova et al, 2000; Heidemann et al, 2003). On the other hand, a recent report suggests that in melanoma cells, CXCL-8-mediated chemotaxis is mainly mediated through CXCR1 (Ramjeesingh et al, 2003).…”

Section: Discussionmentioning

confidence: 89%

CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion

et al. 2009

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The aggressiveness of malignant melanoma is associated with differential expression of CXCL-8 and its receptors, CXCR1 and CXCR2. However, the precise functional role of these receptors in melanoma progression remains unclear. In this study, we investigate the precise functional role of CXCR1 and CXCR2 in melanoma progression. CXCR1 or CXCR2 were stably overexpressed in human melanoma cell lines, SBC-2 (non-tumourigenic) and A375P (low-tumourigenic) exhibiting low endogenous expression of receptors. Functional assays were performed to study the resulting changes in cell proliferation, motility and invasion, and in vivo tumour growth using a mouse xenograft model. Our data demonstrated that CXCR1-or CXCR2-overexpressing SBC-2 and A375P melanoma cells had enhanced proliferation, chemotaxis and invasiveness in vitro. Interestingly, CXCR1 or CXCR2 overexpression in SBC-2 cells induced tumourigenicity, and A375P cells significantly enhanced tumour growth as examined in vivo. Immunohistochemical analyses showed significantly increased tumour cell proliferation and microvessel density and reduced apoptosis in tumours generated from CXCR1-or CXCR2-overexpressing melanoma cells. CXCR1-or CXCR2-induced modulation of melanoma cell proliferation and migration was observed to be mediated through the activation of ERK1/2 phosphorylation.Together, these studies demonstrate that CXCR1 and CXCR2 play essential role in growth, survival, motility and invasion of human melanoma.

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Section: Discussionmentioning

confidence: 89%

CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion

et al. 2009

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“…One consequence of this dysregulated NF-κB activity 23,55-58,61-68 is that there is constitutive transcription of the NF-κB-dependent chemokines CXCL1 and CXCL8 in human tumours [90][91][92][93][94][95][96] . Constitutive expression of these chemokines can transform immortalized melanocytes and is associated with increased metastasis in colon carcinoma, squamous-cell carcinoma and melanoma 19, 28,91,97 .…”

Section: Activation Of Nf-κb Enhances Chemokine Transcriptionmentioning

confidence: 99%

NF-κB, chemokine gene transcription and tumour growth

2002

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The constitutive expression of angiogenic and tumorigenic chemokines by tumour cells facilitates the growth of tumours. The transcription of these angiogenic and tumorigenic chemokine genes is modulated, in part, by the nuclear factor-κB (NF-κB) family of transcription factors. In some tumours, there is constitutive activation of the kinases that modulate the activity of inhibitor of NF-κB (IκB) kinase (IKK), which leads to the constitutive activation of members of the NF-κB family. This activation of NF-κB is associated with the dysregulation of transcription of genes that encode cytokines, chemokines, adhesion factors and inhibitors of apoptosis. In this review, I discuss the factors that lie upstream of the NF-κB cascade that are activated during tumorigenesis and the role of the putative NF-κB enhanceosome in constitutive chemokine gene transcription during tumorigenesis.Chemokines are small, pro-inflammatory peptides; they are often expressed in response to the induction of expression of nuclear factor-κB (NF-κB) by cytokines or other stimuli. Chemokines regulate the transport, activation and, sometimes, proliferation of several cell types, including myeloid, lymphoid, endothelial and epithelial cells 1,2 . There are four chemokine subfamilies -CXC, C, CX 3 C and CC -based on the positions of conserved cysteine residues near the amino terminus of the proteins 1 (TABLE 1). Melanoma growthstimulatory activity (CXCL1) and interleukin-8 (IL-8, CXCL8) are members of the CXCchemokine family, which also includes interferon-γ (IFN-γ)-inducible gene 10 (CXCL10), IFN-inducible T-cell α-chemoattractant (CXCL11), monocyte induced by IFN-γ (CXCL9), epithelial-derived neutrophil-activating peptide 78 (ENA-78, CXCL5), granulocyte chemotactic protein 2 (CXCL6), neutrophil activating peptide 2 (CXCL7), a mitogen for Bcell progenitors known as stromal-derived factor (CXCL12) and B-cell-activating factor 1/Blymphocyte chemoattractant (BCA1/BLC, CXCL13) 1 . The expression of various members of the chemokine superfamily is induced by several cytokines, such as IL-1 and tumour-necrosis factor (TNF), through an NF-κB-mediated event; by IFN-γ through the Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway; or by activating protein 1 (AP1)-mediated transcription. The transcription of chemokine genes is often inhibited by transforming growth factor-β (TGF-β) and glucocorticoids 1 .As the CXC-chemokines CXCL1 and CXCL8 have been associated with tumour growth, metastasis and angiogenesis, I concentrate on these important chemokines. The biological functions of chemokines are mediated through seven-transmembrane G-protein-coupled receptors. CXCL8 and CXCL6 bind to the chemokine receptors CXCR1 and CXCR2, whereas CXCL1 and other CXC-chemokines that have a Glu-Leu-Arg (ELR) motif at their amino terminus (CXCL2, -3 and-5) bind to and activate CXCR2 only 2 . There are also viral receptors Both the CXC-chemokines and their receptors, and the CC-chemokines and their receptors, are involved in ...

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“…One of the most important functions of chemokine receptors is to mediate the chemotactic response of the chemokine receptor-expressing cells (Mehrad et al, 1999), which is essential for the recruitment of leukocytes to inflammatory site (Garcia-Ramallo et al, 2002;Mariani and Panina-Bordignon, 2003) and is likely important for the metastasis of cancer cells (Loukinova et al, 2000;Muller et al, 2001;Mashino et al, 2002). Vesicle recycling of chemokine receptors, including CXCR2, has been implicated in chemotaxis (Perez et al, 1986(Perez et al, , 1987(Perez et al, , 1989Zaslaver et al, 2001).…”

Section: Molecular Biology Of the Cell 2464mentioning

confidence: 99%

“…These results are consistent with the previous data showing the inhibition of the recycling of several other receptors, such as transferrin receptor and M4 muscarinic receptor, by the expression of myosin Vb tail or Rab11-FIP2 (129 -512) Hales et al, 2002;Volpicelli et al, 2002). The inhibition of the receptor recycling is likely due to the condensation of the recycling system induced by the expression of the mutant myosin Vb or Rab11-FIP2 secondary to the exit from the recycling system.One of the most important functions of chemokine receptors is to mediate the chemotactic response of the chemokine receptor-expressing cells (Mehrad et al, 1999), which is essential for the recruitment of leukocytes to inflammatory site (Garcia-Ramallo et al, 2002;Mariani and Panina-Bordignon, 2003) and is likely important for the metastasis of cancer cells (Loukinova et al, 2000;Muller et al, 2001;Mashino et al, 2002). Vesicle recycling of chemokine receptors, including CXCR2, has been implicated in chemotaxis (Perez et al, 1986(Perez et al, , 1987(Perez et al, , 1989Zaslaver et al, 2001).…”

mentioning

confidence: 99%

Rab11-Family Interacting Protein 2 and Myosin Vb Are Required for CXCR2 Recycling and Receptor-mediated Chemotaxis

Fan

Lapierre

Goldenring

et al. 2004

MBoC

128

130

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Agonist-stimulated internalization followed by recycling to the cell membrane play an important role in fine-tuning the activity of chemokine receptors. Because the recycling of chemokine receptors is critical for the reestablishment of the cellular responsiveness to ligand, it is crucial to understand the mechanisms underlying the receptor recycling and resensitization. In the present study, we have demonstrated that the chemokine receptor CXCR2 associated with myosin Vb and Rab11-family interacting protein 2 (FIP2) in a ligand-dependent manner. Truncation of the C-terminal domain of the receptor did not affect the association, suggesting that the interactions occur upstream of the C terminus of CXCR2. After ligand stimulation, the internalized CXCR2 colocalized with myosin Vb and Rab11-FIP2 in Rab11a-positive vesicles. The colocalization lasted for ϳ2 h, and little colocalization was observed after 4 h of ligand stimulation. CXCR2 also colocalized with myosin Vb tail or Rab11-FIP2 (129 -512), the N-terminal-truncated mutants of myosin Vb and Rab11-FIP2, respectively, but in a highly condensed manner. Expression of the enhanced green fluorescent protein-tagged myosin Vb tail significantly retarded the recycling and resensitization of CXCR2. CXCR2 recycling was also reduced by the expression Rab11-FIP2 (129 -512). Moreover, expression of the myosin Vb tail reduced CXCR2-and CXCR4-mediated chemotaxis. These data indicate that Rab11-FIP2 and myosin Vb regulate CXCR2 recycling and receptor-mediated chemotaxis and that passage of internalized CXCR2 through Rab11a-positive recycling system is critical for physiological response to a chemokine. INTRODUCTIONChemokine receptors belong to the large family of seventransmembrane G protein-coupled receptors (GPCRs) that function in immune and inflammatory response by regulating the activation and migration of leukocytes, immune cell development, and angiogenesis (Nagasawa et al., 1996;Luster 1998;Belperio et al., 2000;Murphy et al., 2000;Zlotnik and Yoshie, 2000). Some of them (e.g., CCR5 and CXCR4) participate in HIV infection of CD4 ϩ T lymphocytes as coreceptors (Berger et al., 1999). Ligand binding to the chemokine receptors triggers various signaling cascades, including activation of G proteins, phosphotidylinositol 3-kinase, Janus kinase/signal transducers and activators of transcription proteins, the Rho-p160 ROCK axis, and the MAPK pathway (Wu et al., 1993;Ganju et al., 1998;Mellado et al., 1998;Vicente-Manzanares et al., 1999;Vicente-Manzanares et al., 2002). Chemokine activation of these intracellular signals is often accompanied by chemokine receptor internalization and trafficking back to the cell membrane. The intracellular trafficking of chemokine receptors controls their activities, and the balance between the chemokine receptor recycling and degradation dictates the leukocyte responsiveness to chemokines (Sabroe et al., 1997;Asagoe et al., 1998;Khandaker et al., 1998;Mack et al., 1998).Ligand stimulated chemokine receptor internalization can be accomplished ...

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Growth Regulated Oncogene-α expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC Receptor-2 dependent mechanism

Cited by 161 publications

References 15 publications

CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion

CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion

NF-κB, chemokine gene transcription and tumour growth

Rab11-Family Interacting Protein 2 and Myosin Vb Are Required for CXCR2 Recycling and Receptor-mediated Chemotaxis

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