Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment

N A Syed; J J Windle; S R Darjatmoko; J M Lokken; R A Steeves; R Chappell; I H Wallow; B A Koop; G Mangold; K A Howes; D M Albert

Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment

Journal article

Peer reviewed

Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment

N A Syed, J J Windle, S R Darjatmoko, J M Lokken, R A Steeves, R Chappell, I H Wallow, B A Koop, G Mangold, K A Howes, …

Investigative ophthalmology & visual science, Vol.39(13), pp.2800-2805

12/1998

PMID: 9856795

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Abstract

To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

Immunohistochemistry

Melanoma - metabolism

Uveal Neoplasms - therapy

Melanoma-Specific Antigens

Antigens, Neoplasm

Uveal Neoplasms - pathology

Antigens, Polyomavirus Transforming - metabolism

Membrane Glycoproteins - metabolism

Mice, Inbred C57BL

Male

Mice, Transgenic

S100 Proteins - metabolism

Melanoma - pathology

Neoplasm Proteins - metabolism

Fas Ligand Protein

Animals

In Situ Hybridization

Dacarbazine - pharmacology

Pigment Epithelium of Eye - ultrastructure

Female

Mice

Mice, Inbred BALB C

Uveal Neoplasms - metabolism

Melanoma - therapy

Details

Title: Subtitle: Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment
Creators: N A Syed - Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA
J J Windle
S R Darjatmoko
J M Lokken
R A Steeves
R Chappell
I H Wallow
B A Koop
G Mangold
K A Howes
D M Albert
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.39(13), pp.2800-2805
Publisher: United States
PMID: 9856795
ISSN: 0146-0404
eISSN: 1552-5783
Grant note: EY01917 / NEI NIH HHS
Language: English
Date published: 12/1998
Academic Unit: Pathology; Ophthalmology and Visual Sciences
Record Identifier: 9983979943602771

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