Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1

Reca, Ryan; Mastellos, Dimitrios C.; Majka, Marcin; Marquez, Leah A.; Ratajczak, Janina; Franchini, Silvia; Glodek, Aleksandra M.; Honczarenko, Marek; Spruce, Lynn A.; Janowska‐Wieczorek, Anna; Ratajczak, Mariusz Z.

doi:10.1182/blood-2002-10-3233

Cited by 208 publications

(285 citation statements)

References 60 publications

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“…Because mesenchymal stem cells also migrate to sites of injury as part of the tissue regenerative response, one group of researchers investigated the ability of C3a and C5a to induce similar chemotaxis in mesenchymal stem cells. C3a and C5a promote migration of mesenchymal stem cells, inducing downstream signaling cascades including ERK1/2 and Akt upon binding their receptors (130), results that parallel the finding that C3a exhibits chemotactic influence over hematopoietic progenitor cells (131). In this latter population of stem cells, C3a provides a critical migratory signal leading to their engraftment into bone marrow (131).…”

Section: Complement Proteins Facilitate Invasion and Migrationsupporting

confidence: 64%

“…C3a and C5a promote migration of mesenchymal stem cells, inducing downstream signaling cascades including ERK1/2 and Akt upon binding their receptors (130), results that parallel the finding that C3a exhibits chemotactic influence over hematopoietic progenitor cells (131). In this latter population of stem cells, C3a provides a critical migratory signal leading to their engraftment into bone marrow (131). C3a also provides a chemotactic stimulus for the migration of neural stem cells in several models of murine neurogenesis (132,133).…”

Section: Complement Proteins Facilitate Invasion and Migrationsupporting

confidence: 60%

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Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

219

245

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Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia.

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Section: Complement Proteins Facilitate Invasion and Migrationsupporting

confidence: 64%

Section: Complement Proteins Facilitate Invasion and Migrationsupporting

confidence: 60%

Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

219

245

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“…Activation of osteoclasts and cathepsins has also been implicated in the mobilization of the hematopoietic and endothelial progenitor cells [39,40]. Finally, additional molecules such as extracellular matrix (ECM) compounds, matrix degradation products and activated complement proteins have crucial roles in priming CXCR4 + cells and modulating the amplitude of SDF-1 signals [41][42][43]. Of note, during G-CSF-induced BM cell mobilization, plasma is enriched for soluble molecules that synergize with SDF-1 to attract CXCR4 + cells [43].…”

Section: How Does Activation Of the Sdf-1-cxcr4 Pathway Support Mobilmentioning

confidence: 99%

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

Petit

Jin

Rafii

2007

Trends in Immunology

519

374

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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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“…The complement component C3 is synthesized by bone marrow stromal cells, 91 and on G-CSF administration, C3 is cleaved into C3a and C3b. 92 HSPCs express the receptor for C3a, and binding of C3a augments their chemotaxis to CXCL12.…”

Section: Complement Regulates Mobilizationmentioning

confidence: 99%