A CD36-Binding Peptide from Thrombospondin-1 Can Stimulate Resorption by Osteoclasts in Vitro

Carron, J.A.; Wagstaff, Simon C.; Gallagher, James A.; Bowler, W.B.

doi:10.1006/bbrc.2000.2574

Cited by 28 publications

(18 citation statements)

References 29 publications

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“…The TSP1-CD36 interaction also stimulates resorption by osteoclasts (52) and induces TIMP-1 production and secretion in prostate and breast tumor cell lines (53). In addition, our results now establish that TSP1 promotes prostate tumor cell migration.…”

Section: Discussionsupporting

confidence: 67%

Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors

et al. 2011

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The antitumor effects of pharmacologic inhibitors of angiogenesis are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process. In xenografted tumors, we observed that TSP1 altogether inhibited angiogenesis and fostered tumor development. Our results show that TSP1 is a potent stimulator of prostate tumor cell migration. This effect required CD36, which also mediates TSP1 antiangiogenic activity, and was mimicked by an antiangiogenic TSP1-derived peptide. As suspected for pharmacologic inhibitors of angiogenesis, the TSP1 capacities to increase hypoxia and to trigger cell migration are thus inherently linked. Importantly, although antiangiogenic TSP1 increases hypoxia in vivo, our data show that, in turn, hypoxia induced TSP1, thus generating a vicious circle in prostate tumors. In radical prostatectomy specimens, we found TSP1 expression significantly associated with invasive tumors and with tumors which eventually recurred. TSP1 may thus help select patients at risk of prostate-specific antigen relapse. Together, the data suggest that intratumor disruption of the hypoxic cycle through TSP1 silencing will limit tumor invasion.

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Section: Discussionsupporting

confidence: 67%

Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors

et al. 2011

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“…In terms of efferocytosis, the vitronectin receptor binds to the soluble PS ligand MFG-E8 and mediates a tight connection to the apoptotic cells, thus facilitating their engulfment [17]. CD36 has been reported to be involved in osteoclast-driven bone resorption [18], and its function during efferocytosis is well-established [19][20][21].…”

Section: J U S T a C C E P T E Dmentioning

confidence: 99%

Moonlighting osteoclasts as undertakers of apoptotic cells

et al. 2012

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Rapid clearance of apoptotic cells, frequently referred to as efferocytosis, is crucial for the maintenance of tissue homeostasis and the prevention of autoimmunity. The common model of apoptotic cell clearance involves a system of released "Find me" and exposed "Eat me" signals on apoptotic cells, detected and recognized by matching receptors on macrophages or dendritic cells (DC), referred to as the phagocytic synapse. Osteoclasts share the monocyte lineage with these professional mononuclear phagocytes, thus raising the question if, in addition to bone resorption, osteoclasts can act as scavengers for apoptotic cells. Our qPCR data clearly show that osteoclasts express most of the genes required for dying cell clearance at mRNA levels similar to or even higher than those observed in M1-macrophages, M2-macrophages or DC. Our microscopical analyses reveal that osteoclasts in fact can bind and/or engulf apoptotic cells in an essentially serum-independent fashion. Together with our data on the abundance of the respective mRNAs, these results identify the vitronectin receptor (integrin α(ν)β(3))/milk fat globule-EGF factor 8 protein (MFG-E8) axis, the scavenger receptors (CD36, CD68 and class A macrophage scavenger receptor (SR-A)), the complement/complement receptor axis, the Mer/Tyro3/Protein S axis, and the phosphatidylserine (PS) receptor brain-specific angiogenesis inhibitor 1 (BAI1) as the most promising candidates to be involved in osteoclast-mediated efferocytosis.

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“…In an in vitro model, osteoclast resorption was enhanced on dentin soaked in TSP1 or in CD36-binding TSP peptides (Carron et al, 2000). Like TSP1, TSP2 also contains a C36 binding domain and contains an RGD domain that may be involved in promoting the attachment of osteoclasts.…”

Section: Reduced Bone Resorption In Tsp2-null Micementioning

confidence: 99%

Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice

Hankenson

James

Apone³

et al. 2005

Matrix Biology

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A CD36-Binding Peptide from Thrombospondin-1 Can Stimulate Resorption by Osteoclasts in Vitro

Cited by 28 publications

References 29 publications

Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors

Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors

Moonlighting osteoclasts as undertakers of apoptotic cells

Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice

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