CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications

Abstract

Cancer is a multi-step disease caused by the accumulation of genetic mutations and/or epigenetic changes, and is the biggest challenge around the world. Cytokines, including chemokines, exhibit expression changes and disorders in all human cancers. These cytokine abnormalities can disrupt homeostasis and immune function, and make outstanding contributions to various stages of cancer development such as invasion, metastasis, and angiogenesis. Chemokines are a superfamily of small molecule chemoattractive cytokines that mediate a variety of cellular functions. Importantly, the interactions of chemokine members CXCL12 and its receptors CXCR4 and CXCR7 have a broad impact on tumor cell proliferation, survival, angiogenesis, metastasis, and tumor microenvironment, and thus participate in the onset and development of many cancers including leukemia, breast cancer, lung cancer, prostate cancer and multiple myeloma. Therefore, this review aims to summarize the latest research progress and future challenges regarding the role of CXCL12-CXCR4/CXCR7 signaling axis in cancer, and highlights the potential of CXCL12-CXCR4/CXCR7 as a biomarker or therapeutic target for cancer, providing essential strategies for the development of novel targeted cancer therapies.

Exploration of prognostic and treatment markers in hepatocellular carcinoma via GPCR-related genes analysis

“…Most of the GPCRs included in the risk score model used in this study are either FDA-approved drug targets or drug targets in the phase of clinical trials. Small molecule inhibitors of ACKR3 were manufactured, including CCX771, CCX754 and CCX733 [ 63 ], among which the former two had already shown the capability of reducing nearly half of colorectal carcinoma lung metastases in vivo [ 64 ]. Maraviroc, including CCR5 and CCR3 antagonists, has been approved for the treatment of human immunodeficiency virus (HIV) infection [ 65 ].…”

Effects of Paeoniflorin on Hippocampus and Inflammatory Response in an Acute Myocardial Infarction Anxiety Model Based on CXCL12/CXCR4 Axis

“…CXCL12/CXCR4 axis also plays an important role in the progression of coronary artery disease. CXCR4 positive endothelial progenitor cells promote angiogenesis through CXCL12 signaling and reduce coronary artery stenosis and poor blood flow [13] .…”

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

“…CXCL-12 is important for MM cell evasion of apoptosis and survival by upregulating survivin, B-cell lymphoma (BCL)-2, and ATP-binding cassette (ABCC)-1, a multidrug resistance transporter [154]. Further, CXCL-12 promotes homing of CXCR-4-expressing MM cells to CXCL-12+ stromal niches in the BM and retention through strong adhesion of α4β1 integrin on MMPCs to VCAM-1 in the BM microvasculature [114,155].…”