Suppression of thrombospondin-1 expression during uveal melanoma progression and its potential therapeutic utility

Shoujian Wang, Aneesh Neekhra, Daniel Albert, Christine M. Sorenson, Nader Sheibani

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objectives: To determine whether expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, is downregulated during progression of uveal melanoma and whether administration of TSP1 and/or its antiangiogenic peptides attenuate tumor growth. Methods: Tyrosinase-SV40 T-antigens (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 either by crossing Tyr Tag mice with a line of transgenic mice overexpressing TSP1 in the eye or by administration of TSP1-mimetic peptide with known antiangiogenic, antitumor activity. Tumor areas were measured in histological sections using Optima software (Media Cybernetics, Inc). Results: The Tyr Tag tumors from 3-week-old mice showed significant TSP1 expression, which was dramatically downregulated 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 peptide (100 mg/kg/d). Conclusions: Expression of TSP1 was decreased with the angiogenic switch during progression of uveal melanoma, and TSP1 and/or its antiangiogenic peptides were effective in attenuation of tumor growth. Clinical Relevance: Modulation of TSP1 expression and/or activity may be beneficial in treating uveal melanoma.

Original languageEnglish (US)
Pages (from-to)336-341
Number of pages6
JournalArchives of ophthalmology
Volume130
Issue number3
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

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Thrombospondin 1
Polyomavirus Transforming Antigens
Monophenol Monooxygenase
Neoplasms
Transgenic Mice
Therapeutics
Peptides
Down-Regulation
Uveal melanoma
Cybernetics
Angiogenesis Inhibitors
Growth
Software

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Suppression of thrombospondin-1 expression during uveal melanoma progression and its potential therapeutic utility. / Wang, Shoujian; Neekhra, Aneesh; Albert, Daniel; Sorenson, Christine M.; Sheibani, Nader.

In: Archives of ophthalmology, Vol. 130, No. 3, 01.03.2012, p. 336-341.

Research output: Contribution to journalArticle

Wang, Shoujian ; Neekhra, Aneesh ; Albert, Daniel ; Sorenson, Christine M. ; Sheibani, Nader. / Suppression of thrombospondin-1 expression during uveal melanoma progression and its potential therapeutic utility. In: Archives of ophthalmology. 2012 ; Vol. 130, No. 3. pp. 336-341.
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