The CXCL12 (SDF-1)/CXCR4 chemokine axis: Oncogenic properties, molecular targeting, and synthetic and natural product CXCR4 inhibitors for cancer therapy

Zhou, Yu; Cao, Hanbo; Li, Wenjun; Zhao, Li

doi:10.1016/s1875-5364(18)30122-5

Cited by 57 publications

(48 citation statements)

References 97 publications

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“…3). In fact, it is already used in the clinical practice [263]. Moreover, there is evidence of its potential as adjuvant therapy by sensitizing the tumor to other therapies [262,[264][265][266][267][268].…”

Section: Clinical Implications and Future Trendsmentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemo- and radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironment (TME), which involves stem and differentiated tumor cells, as well as different cell types, such as mesenchymal stem cells, endothelial cells, fibroblasts and cells of the immune system, in addition to the extracellular matrix (ECM), different in composition to the ECM in healthy tissues. CSCs regulate multiple cancer hallmarks through the interaction with cells and ECM in their environment by secreting extracellular vesicles including exosomes, and soluble factors such as interleukins, cytokines, growth factors and other metabolites to the TME. Through these factors, CSCs generate and activate their own tumor niche by recruiting stromal cells and modulate angiogenesis, metastasis, resistance to antitumor treatments and their own maintenance by the secretion of different factors such as IL-6, VEGF and TGF-ß. Due to the strong influence of the CSC secretome on disease development, the new antitumor therapies focus on targeting these communication networks to eradicate the tumor and prevent metastasis, tumor relapse and drug resistance. This review summarizes for the first time the main components of the CSC secretome and how they mediate different tumor processes. Lastly, the relevance of the CSC secretome in the development of more precise and personalized antitumor therapies is discussed.

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Section: Clinical Implications and Future Trendsmentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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“…Therefore, CXCR4 + tumor stem cells can migrate or invade along the SDF‐1 concentration gradient to seed in specific tissues or organs. It has been reported that the activation of adenosine A2A receptor interferes with the interaction of SDF‐1 and CXCR4, and the inhibition of SDF‐1/CXCR4 signaling can be a reliable strategy to manage brain metastasis of malignancies 16 …”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that the activation of adenosine A2A receptor interferes with the interaction of SDF-1 and CXCR4, and the inhibition of SDF-1/CXCR4 signaling can be a reliable strategy to manage brain metastasis of malignancies. 16 Given the crucial roles of A2A receptor and SDF-1/CXCR4 signaling in the regulation of tumor metastasis, we investigated and identified the correlation between them in brain metastasis of lung cancer in this study. We demonstrated that A2A receptor activation suppressed the brain metastasis by implicating the SDF-1/CXCR4 axis and protecting BBB, which might provide more proper therapeutic strategies for the management of brain metastasis.…”

Section: Introductionmentioning

confidence: 99%

Adenosine A2A receptor activation reduces brain metastasis via SDF‐1/CXCR4 axis and protecting blood‐brain barrier

Chen

Zhou

et al. 2020

Molecular Carcinogenesis

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Brain metastasis is a leading cause of death worldwide, but the mechanism involved remains unclear. Stromal cell‐derived factor‐1 (SDF‐1)/C‐X‐C motif chemokine receptor 4 (CXCR4) signaling has been reported to induce the directed metastasis of cancers, and adenosine A2A receptor activation suppresses the SDF‐1/CXCR4 interaction. However, whether A2A receptor activation implicates the SDF‐1/CXCR4 signaling pathway and thus modulates brain metastasis remains unclear. In this study, Western blot was performed to evaluate the protein levels. Cell invasion and migration assays were used to estimate the metastasis ability of PC‐9 cells. The viability of cells was demonstrated by lactate dehydrogenase and cell proliferation assays. And the findings in vitro were further identified in nude mice. Notably, adenosine A2A receptor activation inhibited the proliferation and viability of PC‐9 cells and thus suppressed the brain metastasis. A2A receptor stimulation protected the function of blood‐brain barrier (BBB). The suppression of brain metastasis and the protection of BBB by A2A receptor relied on SDF‐1/CXCR4 signaling, and treatment using A2A receptor agonist and CXCR4 antagonist protected the nude mice from malignancy metastasis in vivo. Adenosine A2A receptor activation suppressed the brain metastasis by implicating the SDF‐1/CXCR4 axis and protecting the BBB.

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“…Our study showed that sitagliptin promoted not only the migration and angiogenesis of endothelial progenitor cells but also the expression of the provascular cytokines SDF-1 and VEGF by endothelial progenitor cells at the mRNA and protein levels. Previous studies have shown that SDF-1 works through its unique receptor CXCR4 (24,25), but it also has a completely independent receptor, CXCR7 (26, 27), which has a different role from CXCR4. To determine which SDF-1 receptor mediates the effects of sitagliptin, after screening for the optimal drug concentration of sitagliptin, we used treated endothelial progenitor cells with sitagliptin in vitro while adding a CXCR4 antagonist or CXCR7 siRNA to block CXCR4 or silence CXCR7 expression, respectively.…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway

Liu

Shi

et al. 2019

Front. Endocrinol.

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Aneurysm (AN) embolization is an important treatment for cerebral aneurysms. The endothelialization of the aneurysm neck is crucial for preventing aneurysm recurrence. Sitagliptin is a therapeutic drug for diabetes that has been reported to have cardiovascular-protective effects. This study investigated the effect of sitagliptin on endothelial progenitor cell (EPC) function and endothelialization of aneurysm necks after embolization. The effect of sitagliptin on aneurysm neck endothelialization was examined using a rat aneurysm embolization model. We isolated EPCs and used CCK-8 (Cell Counting Kit-8) and annexin V/PI to analyze the effect of sitagliptin on the proliferation and apoptosis of EPCs. The effects of sitagliptin on the migration and invasion of EPCs were examined using scratch and Transwell assays. The effect of sitagliptin on the angiogenic ability of EPCs was examined using a sprouting assay. Western blot analysis and ELISA were used to analyze the effect of sitagliptin on the expression of proangiogenic factors in EPCs. The in vivo results indicated that sitagliptin promoted endothelialization of the aneurysm neck and increased circulating EPCs and expression levels of SDF-1 and VEGF in peripheral blood. Sitagliptin promoted the proliferation, migration, invasion, and angiogenic abilities of EPCs. Western blot analysis and ELISA showed that sitagliptin promoted the expression of SDF-1 and VEGF in progenitor endothelial cells. Western blot assays showed that sitagliptin activated the expression of NRF2, which is dependent on the function of CXCR4. Furthermore, sitagliptin promoted progenitor endothelial cell migration, invasion and angiogenesis through the SDF-1/CXCR4/NRF2 signaling pathway. Additionally, progenitor endothelial cells expressed SDF-1 and VEGF. The promotion of endothelialization by sitagliptin provides an additional therapeutic option for preventing the recurrence of AN.

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The CXCL12 (SDF-1)/CXCR4 chemokine axis: Oncogenic properties, molecular targeting, and synthetic and natural product CXCR4 inhibitors for cancer therapy

Cited by 57 publications

References 97 publications

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

Adenosine A2A receptor activation reduces brain metastasis via SDF‐1/CXCR4 axis and protecting blood‐brain barrier

Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway

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