The ELR⁺CXCL chemokines and their receptors CXCR1/CXCR2

Abstract

The long-term efficacy of anti-angiogenesis drugs targeting vascular endothelial growth factor (VEGF) and VEGF receptors in the treatment of renal cell carcinoma (RCC) has been lacking. We have shown that the ELR+CXCL cytokines and their (C-X-C) chemokine receptors, namely CXCR1 and CXCR2, stimulate cancer cell proliferation, tumor inflammation, and angiogenesis. Hence, this essential molecular nexus regulating cancer growth represents a key therapeutic target.

Identification of differentially expressed inflammatory factors in Wilms tumors and their association with patient outcomes

“…CXCL7 as a chemical irritant may induce the directional migration of leukocytes, and is primarily secreted by macrophages, lymphocytes, endothelial cells and fibroblasts. CXCL7, as an important cytokine, is not only involved in a variety of physiological and pathological processes including hemopoiesis and inflammation reaction ( 26 – 30 ), but is also closely associated with the occurrence and development of numerous types of cancer ( 31 – 35 ). However, to the best of our knowledge, the roles of MIF and CXCL7 in WT have not previously been examined.…”

High CXC chemokine receptor 1 level represents an independent negative prognosticator in non-metastatic clear-cell renal cell carcinoma patients

“…Of our particular interest in RCC, which could be treated with anti-angiogenesis agents, CXCR1 was reported to induce the growth of ccRCC. 19 Grepin reported that CXCL7/CXCR1/2 axis promoted tumor cell proliferation and angiogenesis. 18 We have also reported previously that higher CXCR2 expression indicated worse clinical outcomes in non-metastatic ccRCC patients, 21 suggesting activated IL-8/CXCR1/ CXCR2 axis could promote tumor growth and lead to diminished prognosis of ccRCC patients.…”

“…However, as CXCR1 and CXCR2 could present on tumor cells, endothelial cells and neutrophils, which could also direct worse prognosis via tumor cell proliferation, tumor angiogenesis and neutrophils recruitment, respectively, the detailed biology mechanism of CXCR1 expression in ccRCC remained to be explored. 13,18,19 In this study, we analyzed CXCR1 expression within epithelial and stromal area separately, and tried to bring insight into the CXCR1 possible function in ccRCC. Our immunohistochemistry findings showed CXCR1 was mainly expressed within epithelial area, and epithelial expressed CXCR1 presented prognostic value while CXCR1 stromal expression failed.…”

“…However, the detailed function of CXCR1 might differ according to different location CXCR1 expressed. 19 Therefore, validation of CXCR1 expression as a relevant prognostic marker in different compartments of ccRCC with a larger, independent cohort of patients must be urgently performed to extend above-mentioned results.…”

Prognostic and predictive role of intra-tumoral CXCR1 expression in patients receiving tyrosine kinase inhibitors for metastatic clear-cell renal cell carcinoma

“…One such marker, C-X-C motif chemokine receptor 1 (CXCR1) in tumor tissues has been evaluated in in-vitro and retrospective studies. 4,5 However, prospective studies evaluating the role of CXCR1 are lacking. This study aims to evaluate the prognostic and predictive role of intra-tumoral CXCR1 expression in patients receiving tyrosine kinase inhibitors (TKIs) for metastatic clear-cell renal cell carcinoma (mCRCC).…”