Suppression of thrombospondin-1 expression during uveal melanoma progression and its potential therapeutic utility
Abstract
OBJECTIVE: To determine whether expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, is down-regulated during progression of uveal melanoma and if administration of TSP1 and/or its antiangiogenic peptides attenuate tumor growth. METHODS: Tyr-tag transgenic mice were used for evaluation of TSP1 expression during tumor progression using immunohistological methods. The therapeutic potential of TSP1 on tumor progression was evaluated by either crossing Tyr-tag mice to a line of transgenic mice over expressing TSP1 in the eye (Tyr-tag;TSP1), or by administration of TSP1 mimetic peptide with known antiangiogenic, antitumor activity. Tumor areas were measured in histological sections using Optima software. RESULTS: Tyr-tag tumors from 3-week-old mice showed significant TSP1 expression which was dramatically down-regulated in tumors from 12-week-old mice. Furthermore, the development and progression of tumor was significantly delayed in Tyr-tag;TSP1 transgenic mice or Tyr-tag mice receiving TSP1 mimetic peptides (100 mg/Kg/day). CONCLUSIONS AND CLINICAL RELEVANCE: TSP1 expression was decreased with the angiogenic switch during progression of uveal melanoma. TSP1 and/or its antiangiogenic peptides were effective in attenuation of tumor growth. Therefore, modulation of TSP1 expression and/or activity may be beneficial in treatment of uveal melanoma.
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TSP1 expression is downregulated in ocular disease with a neovascular component including diabetic retinopathy and uveal melanoma.
“Its expression is downregulated in ocular disease with a neovascular component including diabetic retinopathy and uveal melanoma [44, 45].”
From Thrombospondin-1, BIM and CFH polymorphisms and response to anti-VEGF treatment in neovascular age- related macular degeneration patients (2024) · cites this paper as [45]
The Results (page not provided) show that TSP1 expression became almost undetectable as the mouse ocular tumor progressed and its blood vessels increased; the Discussion relates this finding to human uveal melanoma. The Introduction reports decreased TSP1 in ocular samples from diabetic rats, but does not establish downregulation specifically in diabetic retinopathy. (LLM, conf=0.86)
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Sorenson, C. M., Gurel, Z., Song, Y.-S., Peterson, K. D., Blodi, B. A., & Sheibani, N. (2024) · PLOS ONE · doi:10.1371/journal.pone.0297135 · Cited by 5 · see citing works
- Authors
- Wang, S.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Wang, Shoujian
- Venue
- Archives of Ophthalmology
- Publisher
- American Medical Association (AMA)
- Published
- 2012-03-01
- Volume
- 130
- Issue
- 3
- Pages
- 336
- ISSN
- 0003-9950 (ISSN-L)
- PMC
- PMC3381901
- OpenAlex
- W2060442775
- Cited by
- 19
- References
- 34
- Citations by year
- 2024: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 2
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1rc4ey021357-01)
- National Eye Institute (RC4-EY021357, R01EY016695, EY-18179, P30-EY-16665, EY21357, R01EY018179, EY16995, P30EY016665)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Veterinary Oncology Research
- Keywords
- thrombospondin-1, uveal melanoma, tumor progression, angiogenesis, anti-angiogenic peptides, angiogenic switch, tumor growth inhibition
- MeSH terms
- Uveal Melanoma, Animals, Disease Models, Animal, Melanoma, Mice, Inbred C57BL, Mice, Transgenic, Neovascularization, Pathologic, Peptides, Uveal Neoplasms, Down-Regulation, Gene Expression Regulation, Neoplastic, Disease Progression, Thrombospondin 1, Mice
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