The Tumor Microenvironment Regulates Retinoblastoma Cell Survival
type: CreativeWork
description: Retinoblastoma (Rb) is the most common intraocular malignancy in children comprising 4% of all pediatric tumors. Early intervention increases survival rates up to 95% in developed countries; being survival rates associated to socio-economic status. Despite the high survival rates in developed countries, preservation of the eye and vision are continuing challenges in the management of Rb. Vitreous seeds constitute the greatest challenge in treatment of Rb. The unique location of these seeds within the vitreous makes them difficult to treat. Viable seeds showed reduced proliferative capacity and metabolism. making the majority refractory to current chemotherapeutics. This prompted the development of new delivery routes for chemotherapeutics, such as intra-ophthalmic artery, intravitreal, and subconjunctival administration. Still ocular salvage rates have not exceeded 70% in over two decades. Novel, safer therapies are required but there is a fundamental lack of knowledge about the biology of the tumor for the development of targeted therapies; the vitreous, as it surrounds the seeds; and the interactions between the vitreous and the seeds. Despite the current understanding of how cancer is a multifaceted disease full of complex cellular and protein interactions (commonly referred to as the tumor microenvironment, TME), the immunology of the vitreous microenvironment and the role it plays in the sustainment of seeds in Rb disease is poorly understood. In this study, we begin investigating Rb tumor cells and how they alter the TME by examination of matrix metalloproteinases, a family of enzymes involved in degradation of the extracellular matrix and tissue remodeling heavily implicated in tumor migration and survival. We identified two gelatinases, MMP-2 and MMP-9, to be expressed in Rb cell lines and demonstrated by pharmacological inhibition and genetic knockdown, a role for these gelatinases in Rb cell migration, invasion, and survival. Additionally, we demonstrated …
abstract: Retinoblastoma (Rb) is the most common intraocular malignancy in children comprising 4% of all pediatric tumors. Early intervention increases survival rates up to 95% in developed countries; being survival rates associated to socio-economic status. Despite the high survival rates in developed countries, preservation of the eye and vision are continuing challenges in the management of Rb. Vitreous seeds constitute the greatest challenge in treatment of Rb. The unique location of these seeds within the vitreous makes them difficult to treat. Viable seeds showed reduced proliferative capacity and metabolism. making the majority refractory to current chemotherapeutics. This prompted the development of new delivery routes for chemotherapeutics, such as intra-ophthalmic artery, intravitreal, and subconjunctival administration. Still ocular salvage rates have not exceeded 70% in over two decades. Novel, safer therapies are required but there is a fundamental lack of knowledge about the biology of the tumor for the development of targeted therapies; the vitreous, as it surrounds the seeds; and the interactions between the vitreous and the seeds. Despite the current understanding of how cancer is a multifaceted disease full of complex cellular and protein interactions (commonly referred to as the tumor microenvironment, TME), the immunology of the vitreous microenvironment and the role it plays in the sustainment of seeds in Rb disease is poorly understood. In this study, we begin investigating Rb tumor cells and how they alter the TME by examination of matrix metalloproteinases, a family of enzymes involved in degradation of the extracellular matrix and tissue remodeling heavily implicated in tumor migration and survival. We identified two gelatinases, MMP-2 and MMP-9, to be expressed in Rb cell lines and demonstrated by pharmacological inhibition and genetic knockdown, a role for these gelatinases in Rb cell migration, invasion, and survival. Additionally, we demonstrated …
author: Goldsmith, Zachary K.
keywords: Ocular immunology, Ocular oncology, Ophthalmology, Retinoblastoma, Tumor biology, Tumor microenvironment, Diseases, Eye Diseases, Medical Cell Biology, Medical Sciences, Medical Specialties, Medicine and Health Sciences, Neoplasms
date published: 2018-12-01T08:00:00Z
date modified: 2026-07-24T05:00:33Z
provider: University of Tennessee Health Science Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Tennessee Health Science Center