CXCL12/CXCR4 signal transduction in diseases and its molecular approaches in targeted-therapy

Mousavi, Ashraf Sadat

doi:10.1016/j.imlet.2019.11.007

Cited by 101 publications

(84 citation statements)

References 358 publications

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“…It is involved in stem or progenitor cell migration during tissue regeneration and repair [13][14][15]. CXCL12 also plays a crucial role in tumor proliferation and invasion as well as in the metastasis of cancerous cells such as those of breast cancer or glioblastoma multiforme (GBM) [16][17][18]. GBM is the most frequent and aggressive primary brain tumor in adults leading to a post-diagnosis survival time around 15 months and a 5-year relative survival rate lower than 5% [19,20].…”

Section: Introductionmentioning

confidence: 99%

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

et al. 2020

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Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therapeutic approach, to control the migration of cancerous cells infiltrated in peri-tumoral tissues similar to those of glioblastoma multiforme (GBM). For this purpose, we prepared Alg/Chit NPs entrapping CXCL12 and characterized them. We demonstrated that Alg/Chit NPs, with an average size of ~250 nm, entrapped CXCL12 with ~98% efficiency for initial mass loadings varying from 0.372 to 1.490 µg/mg NPs. The release kinetic profiles of CXCL12 were dependent on the initial mass loading, and the released chemokine from NPs after seven days reached 12.6%, 32.3%, and 59.9% of cumulative release for initial contents of 0.372, 0.744, and 1.490 µg CXCL12/mg NPs, respectively. Mathematical modeling of released kinetics showed a predominant diffusive process with strong interactions between Alg and CXCL12. The CXCL12-NPs were not toxic and did not promote F98 GBM cell proliferation, while the released CXCL12 kept its chemotaxis effect. Thus, we developed an efficient and tunable CXCL12 delivery system as a promising therapeutic strategy that aims to be injected into a hydrogel used to fill the cavity after surgical tumor resection. This system will be used to attract infiltrated GBM cells prior to their elimination by conventional treatment without affecting a large zone of healthy brain tissue.

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Section: Introductionmentioning

confidence: 99%

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

et al. 2020

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“…Although potential mechanisms capable of sculpting the cellular CXCL12 system such as ligand and receptor dimerization /oligomerization, receptor heteromerization, RGSs, and Grks emerged over recent years, the direct proof if and how these mechanisms dictate the molecular organization of the CXCL12 system in distinct cells still awaits experimental clarification. With the emerging role of ACKR3 and CXCR4 as therapeutic targets central to cancer, cardiovascular diseases, and inflammatory processes (Morein et al, 2020;Mousavi 2020;Wang et al, 2018b) knowledge of these sculpting mechanisms is becoming more and more eminent as they will allow for optimized therapeutic strategies. Finally, we hope that our present review will spark new interest into the function of ACKR3 which, as we feel, partially evaporated with its classification as an atypical chemokine receptor.…”

Section: Discussionmentioning

confidence: 99%

“…A long-hold exemption from this rule was CXCL12 (SDF-1) which was assumed to solely interact with CXCR4. CXCR4 represents a classical GPCR which preferentially binds G i , but also Gα q and Gα 12/13 (Heuninck et al, 2019, for review), subsequently allowing for the activation of various signaling pathways / cascades (Mousavi, 2020, for a recent review). It has been further claimed that CXCR4 would additionally activate arrestin-dependent signaling (see Rigo et al, 2018 for a recent work).…”

Section: Introductionmentioning

confidence: 99%

Functions of the CXCL12 Receptor ACKR3/CXCR7—What Has Been Perceived and What Has Been Overlooked

Koch

Engele

2020

Mol Pharmacol

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“…The CXCL12-CXCR4 axis regulates leukocyte chemotaxis in inflammatory conditions and autoimmune diseases. It has significantly been studied in numerous cancers and autoimmune diseases 42 . This axis modulates effects on cells in an autoimmunity context, which may be important for the development or severity of various diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory bowel diseases, and type 1 diabetes 43 .…”

Section: Discussionmentioning

confidence: 99%

Oral lichen planus interactome reveals CXCR4 and CXCL12 as candidate therapeutic targets

Rivera

Crisóstomo

Peña

et al. 2020

Sci Rep

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Today, we face difficulty in generating new hypotheses and understanding oral lichen planus due to the large amount of biomedical information available. In this research, we have used an integrated bioinformatics approach assimilating information from data mining, gene ontologies, protein-protein interaction and network analysis to predict candidate genes related to oral lichen planus. A detailed pathway analysis led us to propose two promising therapeutic targets: the stromal cell derived factor 1 (CXCL12) and the C-X-C type 4 chemokine receptor (CXCR4). We further validated our predictions and found that CXCR4 was upregulated in all oral lichen planus tissue samples. Our bioinformatics data cumulatively support the pathological role of chemokines and chemokine receptors in oral lichen planus. From a clinical perspective, we suggest a drug (plerixafor) and two therapeutic targets for future research. Oral lichen planus (OLP) is a chronic immunologically mediated disease 1. Histopathological features of OLP include hyperkeratosis, acanthosis, degeneration by liquefaction of the basal keratinocyte layer, and prominent lymphocyte infiltration at the connective tissue-epithelium interface 2. OLP is not a homogeneous clinical entity, but a complex disease. A recent review proposes a new classification of this disease, taking into consideration a set of lesions with similar characteristics, including oral lichenoid contact lesions, oral lichenoid drug reactions, and lichen planus pemphigoides, among others 3 .The clinical findings vary from white reticular plaques to erythema, erosions, ulceration, and hyperkeratotic plaques in the oral mucosa 4. Although reticular lesions are often asymptomatic, burning or pain often accompanies erosive/ulcerative manifestations of OLP. The severity of pain may vary from mild to severe and may even interfere with patients' speech, feeding, and swallowing 4. According to the WHO, this disease has a potential for cancerization 5. This potential is presented in about 1% of patients 6. Despite the efforts in biomedical research, the etiology of OLP is unknown, and its molecular basis is still unclear. This may explain why the treatment is palliative. For these reasons, exploration of the mechanisms that govern the disease's pathophysiological process is needed. A disease is rarely the result of an abnormality in a single gene, but it reflects disturbances in the complex intracellular and intercellular network that links tissue and organ systems 7. Today, we face difficulty in generating new hypotheses and understanding OLP due to the large amount of biomedical information available. Encapsulating that information in an understandable way is one of the current challenges of network-based approaches to the study of human diseases 8. The heterogeneity of pathologies, the difficulty of finding a gene or protein in a certain localization, and the cost involved in experimental studies have led to the development of several in silico approaches for the identification of genes and proteins assoc...

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CXCL12/CXCR4 signal transduction in diseases and its molecular approaches in targeted-therapy

Cited by 101 publications

References 358 publications

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

Functions of the CXCL12 Receptor ACKR3/CXCR7—What Has Been Perceived and What Has Been Overlooked

Oral lichen planus interactome reveals CXCR4 and CXCL12 as candidate therapeutic targets

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