Platelets secrete stromal cell–derived factor 1α and recruit bone marrow–derived progenitor cells to arterial thrombi in vivo

Maßberg, Steffen; Konrad, Ildiko; Schürzinger, Katrin; Lorenz, Michael; Schneider, Simon; Zohlnhoefer, Dietlind; Hoppe, Katharina; Schiemann, Matthias; Kennerknecht, Elisabeth; Sauer, Susanne K.; Schulz, Christian; Kerstan, Sandra; Rudelius, Martina; Seidl, Stefan; Sorge, Falko; Langer, Harald F.; Peluso, Mario; Goyal, Pankaj; Vestweber, Dietmar; Emambokus, Nikla; Busch, Dirk H.; Frampton, Jon; Gawaz, Meinrad

doi:10.1083/jcb1733oia5

Cited by 96 publications

(144 citation statements)

References 33 publications

(74 reference statements)

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“…In addition to SDF-1 released by injured tissues, recent evidence has demonstrated that platelets express and release SDF-1 following cytokine-induced activation in vitro and in vivo during vessel injury [20,34,35]. In thrombocytopenic mice, such as TPO-deficient mice, SDF-1 plasma elevation, in addition to mobilization of pro-angiogenic CXCR4 + VEGFR1 + cells (hemangiocytes) and tissue revascularization are severely impaired.…”

Section: Sdf-1 Is the Primary Chemokine That Supports Mobilization Ofmentioning

confidence: 99%

“…Other crucial integrins mediating the incorporation of EPCs include β2 integrins, lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 [53][54][55]. In addition, Massberg et al have demonstrated that SDF-1 released from platelets supports the recruitment of EPCs and facilitates their adhesion to the injured vascular wall [34]. Finally, membrane-bound KitL (mKitL) in atherosclerotic lesions induces the adhesion and recruitment of EPCs, which could be indirectly driven by the activation of the SDF-1-CXCR4 pathway [54].…”

Section: Arrest Extravasation and Retention At The Neo-angiogenic Sitementioning

confidence: 99%

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The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

Petit

Jin

Rafii

2007

Trends in Immunology

526

382

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Pro-angiogenic bone marrow (BM) cells include subsets of hematopoietic cells that provide vascular support and endothelial progenitor cells (EPCs), which under certain permissive conditions could differentiate into functional vascular cells. Recent evidence demonstrates that the chemokine stromal-cell derived factor-1 (SDF-1, also known as CXCL12) has a major role in the recruitment and retention of CXCR4 + BM cells to the neo-angiogenic niches supporting revascularization of ischemic tissue and tumor growth. However, the precise mechanism by which activation of CXCR4 modulates neo-angiogenesis is not clear. SDF-1 not only promotes revascularization by engaging with CXCR4 expressed on the vascular cells but also supports mobilization of pro-angiogenic CXCR4 + VEGFR1 + hematopoietic cells, thereby accelerating revascularization of ischemic organs. Here, we attempt to define the multiple functions of the SDF-1-CXCR4 signaling pathway in the regulation of neo-vascularization during acute ischemia and tumor growth. In particular, we introduce the concept that, by modulating plasma SDF-1 levels, the CXCR4 antagonist AMD3100 acutely promotes, while chronic AMD3100 treatment inhibits, mobilization of pro-angiogenic cells. We will also discuss strategies to modulate the mobilization of essential subsets of BM cells that participate in neo-angiogenesis, setting up the stage for enhancing revascularization or targeting tumor vessels by exploiting CXCR4 agonists and antagonists, respectively.

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Section: Sdf-1 Is the Primary Chemokine That Supports Mobilization Ofmentioning

confidence: 99%

Section: Arrest Extravasation and Retention At The Neo-angiogenic Sitementioning

confidence: 99%

The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

Petit

Jin

Rafii

2007

Trends in Immunology

526

382

View full text Add to dashboard Cite

show abstract

“…However, the recruitment and proliferation of circulating stem and progenitor cell populations, for example mesenchymal stem cells, endothelial progenitor cells and fibrocytes, have been reported (Schmidt et al, 2003;Zernecke et al, 2005;Jin et al, 2006;Massberg et al, 2006). While it is equally feasible that resident structural cells partake in tissue remodelling, there is an increasing body of evidence from studies of diseases with remodelling phenomena which suggest these processes may be greatly enhanced by the participation of progenitor cells, as they become recruited and undergo in situ proliferation and differentiation according to the micro-environment (Schmidt et al, 2003;Zernecke et al, 2005;Jin et al, 2006;Massberg et al, 2006). Interestingly, platelet-derived SDF-1a has been shown to be necessary for 'hermangioblast' mobilization from the bone marrow (Jin et al, 2006), while platelet P-selectin has been shown to be required for their recruitment to inflamed endothelium in models of atherosclerosis (Massberg et al, 2006).…”

Section: Platelets and Tissue Remodelling Eventsmentioning

confidence: 99%

“…While it is equally feasible that resident structural cells partake in tissue remodelling, there is an increasing body of evidence from studies of diseases with remodelling phenomena which suggest these processes may be greatly enhanced by the participation of progenitor cells, as they become recruited and undergo in situ proliferation and differentiation according to the micro-environment (Schmidt et al, 2003;Zernecke et al, 2005;Jin et al, 2006;Massberg et al, 2006). Interestingly, platelet-derived SDF-1a has been shown to be necessary for 'hermangioblast' mobilization from the bone marrow (Jin et al, 2006), while platelet P-selectin has been shown to be required for their recruitment to inflamed endothelium in models of atherosclerosis (Massberg et al, 2006). Furthermore, smooth muscle progenitor cells have been shown to require chemokine presentation by platelets for efficient recruitment (Zernecke et al, 2005), and platelets are also required for re-epithelialization of damaged corneal tissue (Li et al, 2006), with similar mechanisms occurring in airway wall remodelling in asthma.…”

Section: Platelets and Tissue Remodelling Eventsmentioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well‐characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non‐atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti‐platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases.British Journal of Pharmacology (2007) 152, 987–1002; doi:10.1038/sj.bjp.0707364; published online 2 July 2007

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“…Platelets are also a potent source of SDF1 that may affect the migration of CXCR4-expressing tumour cells and the recruitment of BMDCs to sites of metastasis 95 . Furthermore, platelets express many proand anti-angiogenic factors 96 that could influence the establishment and growth of micrometastases.…”

Section: Box 3 Bone Metastasis: a Specialized Microenvironmentmentioning

confidence: 99%

Microenvironmental regulation of metastasis

2008

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Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves ratelimiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.A variety of stromal cells in the surrounding environment are recruited to tumours, and these not only enhance growth of the primary cancer but also facilitate its metastatic dissemination to distant organs. Cancer cells in an aggressive primary mass are adept at exploiting that particular tissue microenvironment; however, once they leave these favourable surroundings, they must possess traits that will allow them to survive in new environments. In order for a metastasis to occur, the intravasated cancer cell must survive in the circulation, arrive at the target organ (seeding), extravasate into the parenchyma and show persistent growth 1 . Each of these stages is inefficient and some are rate limiting 1,2 . For example, senescence or apoptosis of cancer cells at the stage of entry into the metastatic site prevents the spread of the majority of circulating cells [2][3][4] . Seeding can occur to multiple organs, but metastatic tumours may grow in only one or a few 5 . There is also increasing evidence that in some cases cancer cells can lie dormant for many years, and that seeding may occur several years before diagnosis of the primary tumour [6][7][8][9][10] . In another phenomenon, termed angiogenic dormancy, there is a balance of proliferation and apoptosis that results in micrometastases that do not progress further 11,12 . The microenvironment clearly suppresses NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the malignancy of these potentially metastatic cells 10 , and their re-activation to form a clinically relevant metastasis probably occurs through perturbations in the microenvironment. Nevertheless, despite this evidence for early seeding and dormancy, tumour size and grade are the main predictors of metastasis, and this has been reinforced in recent studies in mouse models 13 and by gene expression analysis that linked large tumour size with metastasis-enhancing gene signatures 14 . It has been hypothesized that this may be due to metastatic re-seeding to primary tumours 15 . If this is the case, nothing is currently known about the underlying mechanisms. Successful metastatic outgrowth thus depends on the cumulative ability of cancer cells to appropriate distinct microenvironments at each step in the metastatic cascade: the primary tumour, systemic circulation and the final metastatic site. In this Review we discuss instruct...

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Platelets secrete stromal cell–derived factor 1α and recruit bone marrow–derived progenitor cells to arterial thrombi in vivo

Cited by 96 publications

References 33 publications

The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Microenvironmental regulation of metastasis

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