The role of CXCL12 in tumor microenvironment

Meng, Wenfang; Xue, Shihang; Chen, Ye

doi:10.1016/j.gene.2017.10.015

Cited by 122 publications

(112 citation statements)

References 49 publications

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“…Since the initial efforts to clone and determine the function of secreted cytokines and chemokines over two decades ago, various studies have highlighted the roles of CXCL12. These roles range from B-cell lymphopoiesis, hematopoietic cell survival and septal defects to HIV and cancer (Cavallero et al, 2015;Domanska et al, 2013;Guyon, 2014;Janssens et al, 2018;Meng et al, 2018;Nagasawa, 2007;Page et al, 2018;Patrussi and Baldari, 2011;Reid et al, 2018). Specifically, in hematopoiesis, CXCL12 acts as a chemoattractant for multiple cells, including B-cells and HSPCs, via its receptor CXCR4, which in itself is expressed to varying degrees by these cell types (Cordeiro Gomes et al, 2016;Ratajczak et al, 2006;Smith-Berdan et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the elevation of CXCL12 upon stress might be a self-preservation mechanism that cells adopt in emergency conditions. Radioprotection by CXCL12 might also be relevant in various cancers, in addition to the established role of CXCL12 in supporting epithelial-to-mesenchymal transition that results in cancer metastasis (Cheng et al, 2018;Cordeiro Gomes et al, 2016;Domanska et al, 2013;Meng et al, 2018;Ratajczak et al, 2006;Shan et al, 2015;Tang et al, 2019;Teicher and Fricker, 2010;Yu et al, 2017;Zhou et al, 2019). Using the inducible mouse model to test this will provide a better understanding of the consequence of elevated CXCL12 in a disease state and enable physicians to create better treatment plans.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of function studies in the mouse by deletion of Cxcl12, or its primary receptor Cxcr4, results in lethality which could at least in part be contributed by defects in hematopoiesis, in addition to other aberrations in cardiac septum formation, neuronal cell migration and vasculogenesis (Ma et al, 1998;Nagasawa et al, 1996;Ratajczak et al, 2006;Tachibana et al, 1998). Perturbation of Cxcl12 has also been associated extensively with B-cell lymphopoiesis (Nagasawa et al, 1996) and various cancers including pancreatic, breast, brain, thyroid, prostate, skin (Ahirwar et al, 2018;Domanska et al, 2013;Goffart et al, 2017;Guo et al, 2016;Liu et al, 2014;Meng et al, 2018;Patrussi and Baldari, 2011;Singh et al, 2004;Teicher and Fricker, 2010;Wald et al, 2013;Werner et al, 2017;Zboralski et al, 2017;Zhang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

Forsberg

2020

Preprint

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C-X-C Motif Chemokine Ligand 12 (CXCL12; aka SDF1) is a major regulator of a number of cellular systems, including hematopoiesis where it influences hematopoietic cell trafficking, proliferation, and survival during homeostasis and upon stress and disease. A variety of constitutive, temporal, ubiquitous and cell-specific loss-of-function models have documented the functional consequences on hematopoiesis upon deletion of Cxcl12. Here, in contrast to loss-of-function experiments, we implemented a gain-offunction approach by generating a dox-inducible transgenic mouse model that enables spatial and temporal overexpression of Cxcl12. We demonstrated that ubiquitous CXCL12 overexpression led to an increase in multipotent progenitors in the bone marrow and spleen. The CXCL12+ mice displayed reduced reconstitution potential as either donors or recipients in transplantation experiments. Additionally, we discovered that Cxcl12 overexpression improved hematopoietic stem and progenitor cell mobilization into the blood, and conferred radioprotection by promoting quiescence.Thus, this new CXCL12+ mouse model provided new insights on major facets of hematopoiesis and serves as a versatile resource for studying CXCL12 function in a variety of contexts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

Forsberg

2020

Preprint

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“…Sdf1, Sema3A and Sema3F are involved in melanoma, multiple myeloma, glioblastoma, neuroblastoma, pancreatic, prostate, ovarian and lung cancers (69)(70)(71). Since these pathways are being proposed as putative therapeutic targets, it may be important to consider that they may antagonize each other and that their functions may not be systematically related to a local organization as a gradient or even linked to attraction and repulsion of migratory cells.…”

Section: Discussionmentioning

confidence: 99%

In vivotopology converts competition for cell-matrix adhesion into directional migration

Bajanca

Gouignard

Colle

et al. 2018

Preprint

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When migrating in vivo, cells are exposed to numerous, and somewhat conflicting, signals: chemokines, repellents, extracellular matrix, growth factors. The roles of several of these molecules have been studied individually in vitro or in vivo but we have yet to understand how cells integrate them. To start addressing this question, we used the cephalic neural crest as a model system and looked at the roles of its best examples of positive and negative signals: stromal-cell derived factor 1 (Sdf1/Cxcl12) and class3-Semaphorins. Our results indicate that Sdf1 and Sema3A antagonistically control cell-matrix adhesion via opposite effects on Rac1 activity at the single cell level. Directional migration at the population level emerges as a result of global Semaphorin-dependent confinement and broad activation of adhesion by Sdf1 in the context of a biased Fibronectin distribution. These results indicate that uneven in vivo topology renders the need for precise distribution of secreted signals mostly dispensable.

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“…Surprisingly, the transcription of CXCR4 was increased by Nanotetrac . Its principal ligand is CXCL12 and CXCL12/CXCR4 signalling is known to stimulate tumour angiogenesis (Meng et al 2018). Furthermore, transcription of CX3CR1 is decreased by Nanotetrac ).…”

Section: Effects On Cytokines and Their Receptorsmentioning

confidence: 99%

Tetrac as an anti-angiogenic agent in cancer

Schmohl

Nelson

Spitzweg

2019

Endocrine-Related Cancer

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The thyroid hormones T3 and T4 have emerged as pro-angiogenic hormones with important implications for cancer management. Endogenous circulating hormone levels may help stimulate cancer progression and limit the effectiveness of anticancer therapy, though clinical data remain inconclusive. The capacity of thyroid hormones to modulate angiogenesis is mediated through non-canonical mechanisms initiated at the cell surface receptor integrin αvβ3. This integrin is predominantly expressed on tumour cells, proliferating endothelial cells and tumour stroma-associated cells, emphasising its potential relevance in angiogenesis and tumour biology. Thyroid hormone/integrin αvβ3 signalling results in the activation of intracellular pathways that are commonly associated with angiogenesis and are mediated through classical pro-angiogenic molecules such as vascular endothelial growth factor. The naturally occurring T4 analogue tetrac blocks the pro-angiogenic actions of thyroid hormones at the integrin receptor, in addition to agonist-independent anti-angiogenic effects. Tetrac reduces endothelial cell proliferation, migration and tube formation through a reduction in the transcription of vascular growth factors/growth factor receptors, hypoxia-inducible factor-1α, pro-angiogenic cytokines and a number of other pro-angiogenic genes, while at the same time stimulating the expression of endogenous angiogenesis inhibitors. It further modulates vascular growth factor activity by disrupting the crosstalk between integrin αvβ3 and adjacent growth factor receptors. Moreover, tetrac disrupts thyroid hormone-stimulated tumour recruitment, differentiation and the pro-angiogenic signalling of tumour stromaassociated mesenchymal stem cells. Tetrac affects tumour-associated angiogenesis via multiple mechanisms and interferes with other cancer cell survival pathways. In conjunction with its low toxicity and high tissue selectivity, tetrac is a promising candidate for clinical application.

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The role of CXCL12 in tumor microenvironment

Cited by 122 publications

References 49 publications

Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

In vivotopology converts competition for cell-matrix adhesion into directional migration

Tetrac as an anti-angiogenic agent in cancer

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