Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and -2
Open accessAbstract
Thrombospondins TSP-1 and TSP-2 are potent endogenous inhibitors of angiogenesis. They inhibit angiogenesis through direct effects on endothelial cell migration, proliferation, survival, and apoptosis and by antagonizing the activity of VEGF. Several of the membrane receptor systems and signal transduction molecules that mediate the effects of TSP-1 and TSP-2 have been elucidated. TSP-1 and TSP-2 exert their direct effects through CD36, CD47, and integrins. Recent data indicate that CD36 and β1 integrins collaborate to transmit the signals that are initiated by TSP-1 and TSP-2. Furthermore, these receptors appear to associate with VEGFR2 to form a platform for the integration of positive and negative signals for angiogenesis. Cross talk between pro- and antiangiogenic signal transduction pathways may enable TSP-1 and TSP-2 to inhibit angiogenesis by antagonizing survival pathways while also activating apoptotic pathways. CD36 and CD47 are both involved in the suppression of nitric oxide (NO). Advances in understanding of the molecular regulation of angiogenesis by TSP have paved the way for innovations in experimental treatment of cancers and will likely continue to offer vast avenues for discovery in other disease processes as well.
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THBS and ANGPTL signaling are known to promote angiogenesis.
“both are known to promote angiogenesis,54,55”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [54]
The Abstract describes TSP-1 and TSP-2 as potent endogenous inhibitors of angiogenesis, contrary to the claim that THBS signaling promotes it. The paper acknowledges proangiogenic effects of TSP-1 in some experimental models, but says those effects are eclipsed in the intact molecule. The supplied passages do not address ANGPTL signaling. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe XENO clusters within the xenograft tissue may be hypoxic because of a lack of vasculature and the wound healing process from the xenograft technique.
“suggesting that the XENO clusters within the xenograft tissue may be hypoxic because of a lack of vasculature and the wound healing process from the xenograft technique.”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [54]
The Therapeutic Opportunities section (page unavailable) links tissue ischemia, angiogenesis, graft revascularization, and healing. It does not examine XENO clusters or say that xenograft-induced wound healing and a lack of vasculature make those clusters hypoxic. (LLM, conf=0.76)
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Cites
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Concepts of extracellular matrix remodelling in tumour progression and metastasis
Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J., & Werb, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-18794-x · Cited by 2,296 · see citing works
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Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice
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Single-cell transcriptomics of human-skin-equivalent organoids
Stabell, A. R., Lee, G. E., Jia, Y., Wong, K. N., Wang, S., Ling, J., Nguyen, S. D., Sen, G. L., Nie, Q., & Atwood, S. X. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112511 · Cited by 30 · see citing works
- Authors
- Lawler, P. R., & Lawler, J.
- Affiliations
- McGill University Health Centre (CA)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Lawler, J.
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-01-31
- Volume
- 2
- Issue
- 5
- Pages
- a006627-a006627
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3331684
- OpenAlex
- W2153078549
- Cited by
- 532
- References
- 2
- Citations by year
- 2026: 21 · 2025: 38 · 2024: 51 · 2023: 34 · 2022: 44 · 2021: 49 · 2020: 49 · 2019: 31 · 2018: 35 · 2017: 32 · 2016: 35 · 2015: 39 · 2014: 45 · 2013: 21 · 2012: 7
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA130895)
- National Cancer Institute (R01CA130895, CA130895)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Keywords
- thrombospondin-1, thrombospondin-2, angiogenesis inhibition, CD36, CD47, beta1 integrin, VEGFR2, signal transduction, endothelial cell apoptosis, endothelial cell survival, nitric oxide, anti-angiogenic therapy, cancer
- MeSH terms
- Thrombospondin 2, Antineoplastic Agents, Cell Movement, Forecasting, Humans, Neoplasms, Neovascularization, Pathologic, Nitric Oxide, Signal Transduction, Antigens, CD, Apoptosis, Thrombospondins, Thrombospondin 1, Angiogenesis Inhibitors, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor A, Endothelial Cells, Cell Proliferation, Proto-Oncogene Proteins c-fyn
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