CXC Chemokine/Receptor Axis Profile and Metastasis in Prostate Cancer

Abstract

In this study, the effects of the CXC chemokine/receptor axis on lymph node and distant metastases of prostate cancer (PC) were analyzed. Further, mRNA expression data of metastatic PC were extracted from the Stand Up To Cancer-Prostate Cancer Foundation Dream Team database and differences between metastatic sites were comprehensively analyzed. CXC chemokine/receptor mRNA expression data of primary PC included in the Cancer Genome Atlas were used to analyze the relationships of CXC chemokine/receptor expression with lymph node metastasis and cancer progression. In metastatic PC, significantly higher expression of ELR + CXC chemokines/receptors and significantly lower expression of ELR − CXC chemokines/receptors were observed in bone metastases relative to lymph node metastases. In primary PC, significantly higher ELR − CXC chemokine/receptor expression and significantly lower ELR + CXC chemokine/receptor expression were observed in patients with lymph node metastasis relative to those without. Multivariate logistic regression analysis identified CXCL10 expression as an independent predictor of lymph node metastasis. Furthermore, the log-rank test results revealed that co-expression of CXCL10/CXCR3 was associated with postoperative recurrence. These findings demonstrate heterogeneous expression of CXC chemokine/receptor genes in primary PC as well as differences in expression patterns according to the metastatic site.

IP-10 (CXCL10) Can Trigger Emergence of Dormant Breast Cancer Cells in a Metastatic Liver Microenvironment

“…This ex vivo finding was supported by clinical data wherein high expression levels of IP-10 significantly correlated with worse survival in patients with stage IV breast cancer as well as increasing tumor grade. The former is also noted in numerous other cancer types, including melanoma (37), colorectal carcinoma (38), hepatocellular carcinoma (39), prostate cancer (40), and lung adenocarcinoma (41). Furthermore, IP-10 showed highest expression in those with TNBC disease and was the most abundant CXCR3 ligand observed in all three settings (e.g.…”

Novel Dormancy Mechanism of Castration Resistance in Bone Metastatic Prostate Cancer Organoids

“…Several studies have shown that the bone microenvironment provides essential WNT, TGFbeta, Notch and FGF pathway signaling [ 47 , 48 , 49 , 50 ]. Nagaya and co-workers identified higher expression of the CXC chemokine signaling genes, including CXCL1, CXCL3, CXCL6, CXCR1 and CXCR2 in prostate cancer bone metastases [ 51 ]. Indeed, we have shown previously that the PCSD1 PDX cells grew significantly faster in the bone niche in vivo as intra-femoral xenografts compared to sub-cutaneous xenografts ([ 20 , 21 ] and Muldong et al, manuscript in preparation).…”

Bioinformatics, Molecular Docking and Experiments In Vitro Analyze the Prognostic Value of CXC Chemokines in Breast Cancer

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