Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in the LHBETATAG mouse model

Maria Elena Jockovich, M. Livia Bajenaru, Yolanda Piña, Fernando Suarez, William J Feuer, M. Elizabeth Fini, Timothy G. Murray

Research output: Contribution to journalArticle

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Abstract

PURPOSE. The aim of this study was to quantify tumor cell proliferation and growth, analyze tumor blood vessel development, and determine the efficacy of antiangiogenic and angiostatic therapy in targeting mature vessels in retinal tumors of the LHBETATAG mouse model for retinoblastoma. METHODS. LHBETATAG mouse retinas were analyzed at 4, 8, 12, and 16 weeks of age. Tumor burden was analyzed by histology; cell proliferation, vessel density, angiogenesis, and vessel maturation were detected by immunofluorescence. To assess the efficacy of mature vessel targeting, 16-week-old mice were treated with single subconjunctival injections of the selective vascular-targeting drug combretastatin A4 prodrug (CA4P) or anecortave acetate, and eyes were analyzed 1 day and 1 week after injection to determine microvessel density and the number of angiogenic and mature vessels. RESULTS. Increased cell proliferation and angiogenesis were detected in the retinal inner nuclear layer (INL) before morphologic neoplastic changes were evident. As tumor size increased, angiogenesis diminished concomitantly with the appearance of mature vessels. Treatment with CA4P and anecortave acetate resulted in significant reductions in total vessel density. However, neither drug reduced the amount of α-smooth muscle actin (SMA)-positive, mature vessels. CONCLUSIONS. Results of this study provide new insight into the relationship between tumor growth and blood vessel development in the LHBETAT AG mouse and establish the framework for defining the selective action of two vessel-targeting drugs against new blood vessels compared with mature blood vessels. These findings suggest a high potential value in targeting the process of angiogenesis in the treatment of children with retinoblastoma.

Original languageEnglish
Pages (from-to)2476-2482
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number6
DOIs
StatePublished - Jun 1 2007

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Retinoblastoma
Vascular Tissue Neoplasms
Blood Vessels
Cell Proliferation
Prodrugs
Drug Delivery Systems
Neoplasms
Retinal Neoplasms
Injections
Growth
Microvessels
Tumor Burden
Fluorescent Antibody Technique
Smooth Muscle
Retina
Actins
Histology
Therapeutics
Pharmaceutical Preparations
anecortave acetate

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Jockovich, M. E., Bajenaru, M. L., Piña, Y., Suarez, F., Feuer, W. J., Fini, M. E., & Murray, T. G. (2007). Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in the LHBETATAG mouse model. Investigative Ophthalmology and Visual Science, 48(6), 2476-2482. https://doi.org/10.1167/iovs.06-1397

Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in the LHBETATAG mouse model. / Jockovich, Maria Elena; Bajenaru, M. Livia; Piña, Yolanda; Suarez, Fernando; Feuer, William J; Fini, M. Elizabeth; Murray, Timothy G.

In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 6, 01.06.2007, p. 2476-2482.

Research output: Contribution to journalArticle

Jockovich, ME, Bajenaru, ML, Piña, Y, Suarez, F, Feuer, WJ, Fini, ME & Murray, TG 2007, 'Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in the LHBETATAG mouse model', Investigative Ophthalmology and Visual Science, vol. 48, no. 6, pp. 2476-2482. https://doi.org/10.1167/iovs.06-1397
Jockovich, Maria Elena ; Bajenaru, M. Livia ; Piña, Yolanda ; Suarez, Fernando ; Feuer, William J ; Fini, M. Elizabeth ; Murray, Timothy G. / Retinoblastoma tumor vessel maturation impacts efficacy of vessel targeting in the LHBETATAG mouse model. In: Investigative Ophthalmology and Visual Science. 2007 ; Vol. 48, No. 6. pp. 2476-2482.
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AU - Feuer, William J

AU - Fini, M. Elizabeth

AU - Murray, Timothy G.

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