@article{54ab3e4a815b491784c8afddb74f102f,
title = "Interstitial retinol-binding protein (IRBP) in retinoblastoma",
abstract = "Interstitial retinol-binding protein (IRBP) is an extracellular glycoprotein that appears to be synthesized by the photoreceptors in the normal retina and may be involved in shuttling retinoids through the interphotoreceptor matrix between the retina and pigment epithelium. The present work demonstrated immunochemically that IRBP of the same molecular weight as normal human IRBP (135,000) was present in three retinoblastomas, irrespective of their degree of differentiation. Tumor 1 was classified as differentiated; Tumors 2 and 3 were classified as poorly differentiated. The level of IRBP in the soluble proteins of Tumor 2 was about 8 times that in Tumor 1 and about one-half that in the soluble proteins (including adhering interphotoreceptor matrix) from a pair of normal retinas from a 31-year-old donor. IRBP occurred in the interstitial space of Tumor 3. Most of the IRBP in this tumor was recovered from the medium in which the undifferentiated cells were dispersed. Incubation of the isolated cells from Tumor 3 in medium containing [3H]leucine demonstrated that [3H]IRBP was secreted into the medium. The [3H]IRBP was immunoreactive with rabbit antibovine IRBP antibodies. It was inferred that the [3H]IRBP was glycosylated because it was bound by immobilized concanavalin A and could be displaced with α-methylmannopyranoside. Since IRBP is not normally found in retinas until the time of photoreceptor differentiation, regulation of its gene may be defective in this malignant neuroectodermal neoplasm. The present findings are relevant to the possible role of retinoids and their binding proteins in neoplastic cells, because they demonstrate for the first time the presence of an extracellular retinoid-binding protein in tumor tissue.",
author = "Bridges, {C. D.B.} and Fong, {S. L.} and Landers, {R. A.} and Liou, {G. I.} and Font, {R. L.}",
note = "Funding Information: Interest in the use of retinoids for cancer prevention has led to many studies designed to investigate the presence of cellular retinoid-binding proteins in tumor cells, including retinoblastomas \[Saari et al., 1978; Chader et al., 1981; see Chytil and Ong (1984) for a review\]. The present findings demonstrate for the first time the occurrence of an extracellular retinoid-binding protein in tumor tissue. Its presence in the interstitital space was established in Tumor 3 by the observation that most of the IRBP in this tumor was recovered from the medium in which the undifferentiated cells had been dispersed rather than from the soluble proteins obtained by homogenizing these cells. Because of its limited availability, it was not possible to establish whether retinoblastoma IRBP contained endogenous retinol, as shown for human IRBP (Fong et al., 1984a). At present, therefore, the extent of its role in the transport, functioning and utilization of retinoids within the tumor remains to be determined. Like mature bovine, rat, monkey and human retinas (Fong et al., 1984a, b: Gonzalez-Fernandez el al., 1984, 1985; Wiggert et ell., 1984), as well as the piece of unaffected retina examined in the present study, the cells from Tumor 3 synthesized and secreted IRBP in dtro. The fluorograms of the medium in which this incubation had been carried out showed that IRBP was the major soluble protein secreted. IRBP from normal vertebrate eyes is a glycoprotein (Liou et al., 1982; Adler and Evans, 1983; Fong el al., 1984a, b: Gonzalez-Fernandez et al., 1984). It is concluded that the \[3H\]IRBP synthesized by the retinoblasts was also glycosylated because it was retained on a column of immobilized concanavalin A and could be eluted with a competing sugar. However, the small quantity of retinoblastoma IRBP available did not permit comparison of its oligosaccharide composition with that of IRBP purified from normal human eyes. Proteins that are considered to be characteristic of both glial and neuronal cells have been detected immunohistochemically in retinoblastomas (Molnar et al., 1982; Messmer et al., 1985) and in cultured Y79 and WERI-Rbl human retinoblastoma cell lines (Jiang et al,, 1984; Kyritsis et al., 1984). Nevertheless, cellular retinal binding protein, which is expressed in the neuroglial (Muller) cells of the mature retina (Bunt-Milam and Saari, 1983), has not been detected in Y79 or WERI-Rbl cells (Saari et al., 1978). although two other cellular retinoid-binding proteins are present in these cultured lines (Saari et al., 1978: Chader et al., 1981). Cells from fresh tumors may not be strictly comparable with those in cultured lines, but these results suggest that undifferentiated reti-noblasts are able to express the gene for a glycoprotein that is expected to be lbund only in retinoblastomas exhibiting areas of photoreceptor differentiation. We conclude, therefore, that regulation of the gene for IRBP may be defective in these malignant cells. Acknowledgements--This work was supported by the Retina Research Foundation of Houston, the Knights Templar Eye Foundation Inc., an unrestricted departmental grant from the National Council for the Prevention of Blindness and grants from the National Institutes of Health (National Eye Institute). Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",
year = "1985",
doi = "10.1016/0197-0186(85)90044-0",
language = "English (US)",
volume = "7",
pages = "875--881",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",
number = "5",
}