Mechanism and biological significance of constitutive expression of MGSA/GRO chemokines in malignant melanoma tumor progression

Luan, Jing; Shattuck-Brandt, Rebecca L.; Haghnegahdar, Hamid; Owen, James D.; Strieter, Robert M.; Burdick, Marie D.; Nirodi, Chaitanya S.; Beauchamp, Dan E.; Johnson, Kimberly N.; Richmond, Ann

doi:10.1002/jlb.62.5.588

Cited by 188 publications

(171 citation statements)

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“…Moreover, depending on disease status, the concentrations of CXCL1 measured in biological fluids of humans or animal models do not exceed 10 ng/ml (18,54,55). Therefore, using a narrower range of concentrations of CXCL1 to examine its effect on ASMC migration may better reflect its biological significance in asthmatic airways remodeling.…”

Section: Discussionmentioning

confidence: 99%

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

Al-Alwan

Chang

Rousseau

et al. 2014

The Journal of Immunology

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Airway smooth muscle cell (ASMC) migration is an important mechanism postulated to play a role in airway remodeling in asthma. CXCL1 chemokine has been linked to tissue growth and metastasis. In this study, we present a detailed examination of the inhibitory effect of CXCL1 on human primary ASMC migration and the role of the decoy receptor, Duffy AgR for chemokines (DARC), in this inhibition. Western blots and pathway inhibitors showed that this phenomenon was mediated by activation of the ERK-1/2 MAPK pathway, but not p38 MAPK or PI3K, suggesting a biased selection in the signaling mechanism. Despite being known as a nonsignaling receptor, small interference RNA knockdown of DARC showed that ERK-1/2 MAPK activation was significantly dependent on DARC functionality, which, in turn, was dependent on the presence of heat shock protein 90 subunit α. Interestingly, DARC- or heat shock protein 90 subunit α–deficient ASMCs responded to CXCL1 stimulation by enhancing p38 MAPK activation and ASMC migration through the CXCR2 receptor. In conclusion, we demonstrated DARC’s ability to facilitate CXCL1 inhibition of ASMC migration through modulation of the ERK-1/2 MAPK–signaling pathway.

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Section: Discussionmentioning

confidence: 99%

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

Al-Alwan

Chang

Rousseau

et al. 2014

The Journal of Immunology

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“…Furthermore, depletion of CXCL1, 2, or 3 in the hosts resulted in marked attenuation of tumour-associated angiogenesis and inhibition of tumour growth (101,102).…”

Section: Chemokine-induced Angiogenesis In Tumour Modelsmentioning

confidence: 99%

“…CXCL1, CXCL2, and CXCL3 have all been found to be highly expressed in human melanoma, and when transfected into immortalized murine melanocytes that otherwise do not form tumours, they transformed the phenotype to one of anchorage-independent growth in vitro and the ability to form highly vascular tumours in vivo (101,102). Furthermore, depletion of CXCL1, 2, or 3 in the hosts resulted in marked attenuation of tumour-associated angiogenesis and inhibition of tumour growth (101,102).…”

Section: Chemokine-induced Angiogenesis In Tumour Modelsmentioning

confidence: 99%

Chemokines as mediators of angiogenesis

Mehrad¹,

Keane²,

Strieter³

2007

Thromb Haemost

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180

145

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SummaryChemokines were originally described as cytokines that mediate leukocyte recruitment to sites of inflammation. Members of a subgroup of chemokines, the CXC family, also play a critical role in both physiologic and pathologic angiogenesis, including in the context of chronic inflammation, fibrosis, and malignancy. A unique feature of this family of cytokines is that, on the basis of their structure and receptor binding, individual ligands display either angiogenic or angiostatic biological activity in the regulation of angiogenesis. In this review, we summarize the key literature in this growing field.

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“…The expression of CXCR1 and CXCR2 has been detected in melanoma tumours, which indicates that melanoma cells might be targets for autocrine stimulation by CXCL8 (REF. 9). However, some melanoma tumour cell lines express CXCR4, CCR7 and CCR10, but no detectable levels of other chemokine receptors 6 .…”

Section: Regulation Of Expression Of Chemokine Receptorsmentioning

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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Mechanism and biological significance of constitutive expression of MGSA/GRO chemokines in malignant melanoma tumor progression

Cited by 188 publications

References 0 publications

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

Chemokines as mediators of angiogenesis

NF-κB, chemokine gene transcription and tumour growth

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