Cartilage Oligomeric Matrix Protein (Thrombospondin-5) Is Expressed by Human Vascular Smooth Muscle Cells

Riessen, Reimer; Fenchel, Michael; Chen, Hui; Axel, Dorothea I.; Karsch, Karl R.; Lawler, Jack

doi:10.1161/01.atv.21.1.47

Cited by 114 publications

(108 citation statements)

References 38 publications

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“…This antiapoptotic effect is not cell type-specific and was found to occur in 293 cells, HeLa cells, and primary human chondrocytes. Given that COMP is expressed at sites other than connective tissue, such as vascular smooth muscle, synovium, skin, bone, pancreas, and liver (23,(41)(42)(43)(44)(45), this antiapoptotic effect may have broad implications for cell survival throughout the body. Interestingly, whereas the wild type COMP protein is able to block apoptosis, mutant COMP proteins found in the human diseases multiple epiphysial dysplasia and PSACH have been found to promote apoptosis (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

“…It can inhibit cell proliferation (21), enhance attachment of cells to surfaces (23,24), regulate motility (23), and regulate apoptosis (Refs. 21 and 25-27 and data presented here).…”

Section: Discussionmentioning

confidence: 99%

“…As such it has been proposed that COMP may directly interact with cells. COMP has been shown to aid in the attachment of cells to surfaces (23,24) and does so via an interaction with integrins (24). A COMP mutation in the type 3 repeat, which occurs in 30% of patients with PSACH, abolishes the ability of COMP to aid in attachment (24).…”

mentioning

confidence: 99%

“…A COMP mutation in the type 3 repeat, which occurs in 30% of patients with PSACH, abolishes the ability of COMP to aid in attachment (24). It has also been shown that COMP supports the migration of cells in vitro (23). In terms of the extracellular matrix protein, it is presumed that COMP may play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin.…”

mentioning

confidence: 99%

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Cartilage Oligomeric Matrix Protein Protects Cells against Death by Elevating Members of the IAP Family of Survival Proteins

Gagarina

Carlberg

Mouriès

et al. 2008

Journal of Biological Chemistry

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Cartilage oligomeric matrix protein (COMP) is a component of cartilage, synovium, ligament, and tendon, yet its normal function is largely unknown. To identify its function we have expressed it in 293 and HeLa cell lines and in primary human chondrocytes. We find that COMP protects these cells against death, either in the presence or absence of tumor necrosis factor ␣ and is able to block activation of caspase 3, a critical effector caspase. This effect appears to be mediated by the IAP (inhibitor of apoptosis protein) family of anti-apoptotic proteins because the levels of XIAP, survivin, cIAP1 and cIAP2 are significantly elevated in the COMP-expressing cells and down-regulation of survivin and XIAP protein levels by small interfering RNAs blocks the ability of COMP to enhance survival. The mRNAs for most of the IAP family members were not increased by COMP, indicating that a translational/post-translational mechanism was involved in their induction. However, in both HeLa cells and chondrocytes, COMP induced survivin mRNA by 5-fold. Thus survivin is the first gene identified to be up-regulated transcriptionally by COMP. The carboxyl-terminal half of the protein comprising the type 3 repeats and the RGD sequence (CaCTD domain) was sufficient to promote survival and to elevate the IAPs. Further, an RGD peptide was able to block the prosurvival effect of COMP and the induction of XIAP and survivin, indicating that survival is likely mediated through integrin signaling. These data point to a new role for COMP in protecting cells against death.

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Section: Discussionmentioning

confidence: 99%

“…It can inhibit cell proliferation (21), enhance attachment of cells to surfaces (23,24), regulate motility (23), and regulate apoptosis (Refs. 21 and 25-27 and data presented here).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cartilage Oligomeric Matrix Protein Protects Cells against Death by Elevating Members of the IAP Family of Survival Proteins

Gagarina

Carlberg

Mouriès

et al. 2008

Journal of Biological Chemistry

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“…Cartilage oligomeric matrix protein (COMP)/thrombospondin-5 is a glycoprotein distributed abundantly in cartilage [5], tendon [2], synovium [3,11] and vascular smooth muscle [12]. Structurally, the mature protein is a pentamer of identical subunits that are joined at their N-terminal domains via disulfide linkages, forming a bouquet-like structure.…”

mentioning

confidence: 99%

Gene and Protein Expression of Cartilage Oligomeric Matrix Protein Associated with Oncogenesis in Canine Tumors

Yamanokuchi

Yabuki

Yoshimoto

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. To investigate the expression of cartilage oligomeric matrix protein (COMP) associated with oncogenesis, samples of serum and tumor tissue were obtained from 25 dogs with tumors. The serum levels of COMP in dogs with tumors were significantly higher than in 38 normal controls and correlated with the concentrations of tumor tissue extracts. Positive bands to COMP antibody were detected on immunoblots of tumor extracts. Immunohistochemistry and in situ hybridization demonstrated positive signals of COMP and its mRNA in the cytoplasm of tumor cells from mammary gland tumors, but not in the normal mammary gland. Positive immunohistochemistry results were also obtained for COMP in mast cell tumor and melanoma cells. Oncogenesis might augment production of COMP and the serum level of COMP in dogs.

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Genetic Modulation of Vulnerable Plaques

Dong¹,

Goldschmidt‐Clermont²

2006

The Vulnerable Atherosclerotic Plaque

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Cartilage Oligomeric Matrix Protein (Thrombospondin-5) Is Expressed by Human Vascular Smooth Muscle Cells

Cited by 114 publications

References 38 publications

Cartilage Oligomeric Matrix Protein Protects Cells against Death by Elevating Members of the IAP Family of Survival Proteins

Cartilage Oligomeric Matrix Protein Protects Cells against Death by Elevating Members of the IAP Family of Survival Proteins

Gene and Protein Expression of Cartilage Oligomeric Matrix Protein Associated with Oncogenesis in Canine Tumors

Genetic Modulation of Vulnerable Plaques

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