CXCL8 and Its Cognate Receptors in Melanoma Progression and Metastasis

Abstract

The incidence of melanoma is rising at an alarming rate and we are still awaiting an effective treatment for this malignancy. In its early stage, melanoma can be cured by surgical removal, but once metastasis has occurred there is no effective treatment. Recent findings have suggested multiple functional implications of CXCL8 and its cognate receptors, CXCR1 and CXCR2, in melanoma pathogenesis, thus underscoring their importance as targets for cancer therapy. This review provides an update on the roles of CXCL8 and its receptors in melanoma progression and metastasis. Keywords CXCL8; CXCR1; CXCR2; melanoma Chemokines are secreted, low-molecular-weight chemotactic proteins (8-11 kDa) that regulate the trafficking of leukocytes to inflammatory sites. There are more than 50 chemokines and over 20 chemokine receptors characterized, to date [1]. Chemokines have conserved cysteine residues that play important roles in their structural conformation and function. Structurally, chemokines are divided into four families based upon the position of their conserved two Nterminal cysteine-residues (CXC, CC, C and CX 3 C) [1,2]. Members of the CXC contain one amino acid between the first and second cysteine residues, CC chemokines have adjacent cysteine residues, the C subfamily has only one cysteine residue and CX 3 C chemokines have

Lactobacillus plantarum Lipoteichoic Acid Alleviates TNF-α-Induced Inflammation in the HT-29 Intestinal Epithelial Cell Line

“…IL-8 acts as a chemotactic factor that attracts neutrophils and basophils to the lesion. In addition, it plays important roles in angiogenesis, metastasis, and inflammation (Singh et al, 2010). IL-8 binds to both the CXCR1 and CXCR2 receptors with similar affinity and initiates down-stream signaling cascades.…”

Signaling Pathways Altered During the Metastatic Progression of Melanoma

“…In one case, the induction of CXCL8 expression by ultraviolet-B radiation potentiated tumor and metastasis development. In addition, metastatic melanoma cell lines express higher levels of CXCL8 than its non-metastatic variants [110]. Moreover, in an analysis of tumor specimens, it was seen that radial growth tumors do not present CXCL8 expression, while half of the vertical growth tumors present it.…”

“…Chemokines realize its biological function through the binding in chemokine receptors, G-protein coupled receptors. It has been seen by several authors that melanoma cells have a high expression of chemokines and that its interaction with its receptors stimulates tumor growth, angiogenesis and metastasis [110].…”

Norepinephrine Promotes the β1-Integrin–Mediated Adhesion of MDA-MB-231 Cells to Vascular Endothelium by the Induction of a GROα Release

“…Proinflammatory chemokines, as delivered by macrophages, regulate the site at which leukocytes leave the blood stream by the activation of integrin-mediated adhesion (17,18), and a similar role has been attributed to chemokines for the localization of metastases in several types of cancer (19). CXC chemokines, such as CXCL8/IL-8 and CXCL1/GROa, bind to the G-protein-coupled receptors, CXCR1 and CXCR2, which are described to play an important role with regard to disease progression and metastasis formation (20). In colorectal cancers, GROa expression was shown to be positively associated with tumor size, stage, invasion, lymph node metastasis, and patient survival (21).…”