Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.

Verification that cell lines used for cancer research are derived from malignant cells in primary tumors is imperative to avoid invalidation of study results. Retinoblastoma is a childhood ocular tumor that develops from loss of functional retinoblastoma protein (pRb) as a result of genetic or epige...

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Main Authors: Wesley S Bond, Patricia Y Akinfenwa, Laszlo Perlaky, Mary Y Hurwitz, Richard L Hurwitz, Patricia Chévez-Barrios
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3691222?pdf=render
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spelling doaj-819d2912a5034febb5732eb36c2c9ce02020-11-25T01:17:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6351910.1371/journal.pone.0063519Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.Wesley S BondPatricia Y AkinfenwaLaszlo PerlakyMary Y HurwitzRichard L HurwitzPatricia Chévez-BarriosVerification that cell lines used for cancer research are derived from malignant cells in primary tumors is imperative to avoid invalidation of study results. Retinoblastoma is a childhood ocular tumor that develops from loss of functional retinoblastoma protein (pRb) as a result of genetic or epigenetic changes that affect both alleles of the RB1 gene. These patients contain unique identifiable genetic signatures specifically present in malignant cells. Primary cultures derived from retinoblastoma tumors can be established as non-adherent tumorspheres when grown in defined media or as attached monolayers when grown in serum-containing media. While the RB1 genotypes of tumorspheres match those of the primary tumor, adherent cultures have the germline RB1 genotype. Tumorspheres derived from pRb-negative tumors do not express pRb and express the neuroendocrine tumor markers synaptophysin and microtubule-associated protein 2 (MAP2). Adherent cells are synaptophysin-negative and express pRb, the epithelial cell marker cytokeratin that is expressed in the retinal pigmented epithelium and the vascular endothelial cell marker CD34. While tumorspheres are of malignant origin, our results cast doubt on the assumption that adherent tumor-derived cultures are always valid in vitro models of malignant cells and emphasize the need for validation of primary tumor cultures.http://europepmc.org/articles/PMC3691222?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Wesley S Bond
Patricia Y Akinfenwa
Laszlo Perlaky
Mary Y Hurwitz
Richard L Hurwitz
Patricia Chévez-Barrios
spellingShingle Wesley S Bond
Patricia Y Akinfenwa
Laszlo Perlaky
Mary Y Hurwitz
Richard L Hurwitz
Patricia Chévez-Barrios
Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.
PLoS ONE
author_facet Wesley S Bond
Patricia Y Akinfenwa
Laszlo Perlaky
Mary Y Hurwitz
Richard L Hurwitz
Patricia Chévez-Barrios
author_sort Wesley S Bond
title Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.
title_short Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.
title_full Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.
title_fullStr Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.
title_full_unstemmed Tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.
title_sort tumorspheres but not adherent cells derived from retinoblastoma tumors are of malignant origin.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description Verification that cell lines used for cancer research are derived from malignant cells in primary tumors is imperative to avoid invalidation of study results. Retinoblastoma is a childhood ocular tumor that develops from loss of functional retinoblastoma protein (pRb) as a result of genetic or epigenetic changes that affect both alleles of the RB1 gene. These patients contain unique identifiable genetic signatures specifically present in malignant cells. Primary cultures derived from retinoblastoma tumors can be established as non-adherent tumorspheres when grown in defined media or as attached monolayers when grown in serum-containing media. While the RB1 genotypes of tumorspheres match those of the primary tumor, adherent cultures have the germline RB1 genotype. Tumorspheres derived from pRb-negative tumors do not express pRb and express the neuroendocrine tumor markers synaptophysin and microtubule-associated protein 2 (MAP2). Adherent cells are synaptophysin-negative and express pRb, the epithelial cell marker cytokeratin that is expressed in the retinal pigmented epithelium and the vascular endothelial cell marker CD34. While tumorspheres are of malignant origin, our results cast doubt on the assumption that adherent tumor-derived cultures are always valid in vitro models of malignant cells and emphasize the need for validation of primary tumor cultures.
url http://europepmc.org/articles/PMC3691222?pdf=render
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