The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer

Vandercappellen, Jo; Damme, Jozef Van; Struyf, Sofie

doi:10.1016/j.cytogfr.2010.10.011

Cited by 141 publications

(144 citation statements)

References 167 publications

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“…G-protein-coupled receptors and cell surface glycosaminoglycans (GAGs) (14,32,33) are implicated in the aforementioned functions. One of the major physiological roles of high affinity binding to heparin appears to be the neutralization of the anticoagulant activities on the endothe-lial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation at sites of vascular injury (23,34).…”

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confidence: 99%

“…CXCL4 secreted from stimulated platelet exhibits a wide range of functions such regulation of hematopoiesis (19) and atherosclerosis (20 -22), antiangiogenesis (22)(23)(24)(25), chemotaxis (10,17), thrombocytopenia (26,27), anti-microbial activity (28,29), and inhibition of HIV-1 infection (30,31). G-protein-coupled receptors and cell surface glycosaminoglycans (GAGs) (14,32,33) are implicated in the aforementioned functions.…”

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confidence: 99%

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Alternative C-Terminal Helix Orientation Alters Chemokine Function

Kuo

Chen

Liu

et al. 2013

Journal of Biological Chemistry

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Background: CXCL4L1 is a highly potent anti-angiogenic and anti-tumor chemokine, and its structural information is unknown. Results: CXCL4L1 x-ray structure is determined, and it reveals a previously unrecognized chemokine structure adopting a novel C-terminal helix conformation. Conclusion:The alternative helix conformation enhances the anti-angiogenic activity of CXCL4L1 by reducing the glycosaminoglycan binding ability. Significance: Chemokine C-terminal helix orientation is critical in regulating their functions.

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confidence: 99%

mentioning

confidence: 99%

Alternative C-Terminal Helix Orientation Alters Chemokine Function

Kuo

Chen

Liu

et al. 2013

Journal of Biological Chemistry

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“…Further, PF-4 has pro-thrombotic activity by binding heparin, but it can also function as an anti-coagulant via the generation of activated protein C [23]. However, in PF-4 knock-out mice, occlusive thrombi developed more slowly, whereas PF-4 infusion restored thrombus formation, indicating that this chemokine is rather pro-thrombotic [3]. In view of the high concentrations required for these effects, it remains to be seen whether PF-4var released into the circulation at much lower concentrations is implicated in coagulation and thrombogenesis.…”

Section: Discussionmentioning

confidence: 94%

“…Platelet-derived chemokines, including PF-4, are also implicated in several aspects of vascular biology [1,15], such as monocyte arrest on endothelial cells (in cooperation with RANTES), induction of atherosclerotic lesions [12], promotion of thrombosis [3] and heparin-induced thrombocytopenia [16]. The role of PF4var in processes related to atherosclerosis has, however, not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

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PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with preserved left ventricular function

Sutter

Veire

Struyf

et al. 2013

European Heart Journal

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Background: Platelet-derived chemokines are implicated in several aspects of vascular biology. However, for the chemokine platelet factor 4 variant (PF-4var/CXCL4L1), released by platelets during thrombosis and with different properties as compared to PF-4/CXCL4, its role in heart disease is not yet studied. We evaluated the determinants and prognostic value of the platelet-derived chemokines PF-4var, PF-4 and RANTES/CCL5 in patients with stable coronary artery disease (CAD).

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The prognostic significance of circulating serum amyloid A and CXC chemokine ligand 4 in osteosarcoma

Flores

Kelly

et al. 2017

Pediatric Blood & Cancer

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BACKGROUND Osteosarcoma is the most common pediatric bone cancer. Despite advances in treatment regimens, the survival rate remains 60–70%. There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. PROCEDURE Our lab has previously identified that circulating Serum Amyloid A (SAA) and CXC Chemokine Ligand 4 (CXCL4) are upregulated in patients with osteosarcoma. In this study, we tested if they could be used as prognostic biomarkers. We used ELISAs to measure their concentrations in serum samples (n = 233), and immunohistochemistry to examine expressions in primary tumors (n = 37). Prognostic significance of the serum concentrations and tumor expressions of the biomarkers was then evaluated. RESULTS Patients with “High SAA” and “Low CXCL4” circulating levels at diagnosis significantly correlated with a worse outcome (HR = 1.68, p = 0.014), which was independent of the metastatic status. These patients also exhibited a significantly higher rate of poor histological response to chemotherapy. Furthermore, low tumor expression of CXCL4 correlated with poor survival (HR = 3.57, p = 0.005). CONCLUSIONS Our results demonstrate that circulating SAA and CXCL4 may serve as prognostic biomarkers in osteosarcoma. Targeting CXCL4 has been reported, suggesting that it may be exploited as a therapeutic target in osteosarcoma.

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The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer

Cited by 141 publications

References 167 publications

Alternative C-Terminal Helix Orientation Alters Chemokine Function

Alternative C-Terminal Helix Orientation Alters Chemokine Function

PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with preserved left ventricular function

The prognostic significance of circulating serum amyloid A and CXC chemokine ligand 4 in osteosarcoma

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