Anti-LFA-1 antibodies enhance metastasis of ocular lymphoma to the brain and contralateral eye
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- 作者：Jacob Hochman (1)
DeFen Shen (2)
Michael M. Gottesman (3)
Chi-Chao Chan (2) - 关键词：Metastasis ; Lymphoma ; Eye ; Brain ; LFA ; 1
- 刊名：Clinical & Experimental Metastasis
- 出版年：2013
- 出版时间：January 2013
- 年：2013
- 卷：30
- 期：1
- 页码：91-102
- 全文大小：862KB
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DeFen Shen (2)
Michael M. Gottesman (3)
Chi-Chao Chan (2)
1. Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel
2. Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892-1857, USA
3. Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA - ISSN：1573-7276
文摘
Previously we demonstrated that intraperitoneal (IP) inoculation of Rev-2-T-6 mouse lymphoma into syngeneic Balb/c hosts resulted in brain metastasis, migration along the optic nerve sheath, and ocular infiltration. In a second model: intravitreal inoculation of Rev-2-T-6 cells, the developing lymphoma was largely confined within the eye, seldom breaching the retinal pigment epithelium to reside in the choroid and sclera. There was no retrograde infiltration into the brain. Here, we describe a third, complementary model, whereby intravitreal inoculation of Rev-2-T-6 cells into Balb/c mice, followed by repeated IP inoculations of anti-LFA-1/CD11a monoclonal antibodies, results in extensive infiltration of the choroid, sclera, conjunctiva, eyelids and orbit. Furthermore, the lymphoma cells metastasize along the optic nerve sheath into the brain, and through the contralateral optic nerve tract into the contralateral eye. There is no systemic involvement of the lymphoma. Furthermore, anti-LFA-1 treatment results in elevated levels of serum anti-Rev-2-T-6 antibodies. Inoculation of Rev-2-T-6 cells into the vitreous of severe combined immune deficient mice demonstrates a course of clinical signs and histopathological findings similar to those in immune-competent mice treated with anti-LFA-1 antibodies, including invasion of the contralateral eye. Taken together, these findings suggest that confinement of Rev-2-T-6 lymphoma cells to the eye depends on active immune surveillance using a population of effector cells expressing the cell surface integrin LFA-1. Impairing this protection enhances tumor aggressiveness within the eye, and the likelihood of early retrograde lymphoma metastasis into the brain and the contralateral eye.