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Molecular and Cellular Biology, December 2009, p. 6268-6282, Vol. 29, No. 23
0270-7306/09/$08.00+0     doi:10.1128/MCB.00374-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Changes in Retinoblastoma Cell Adhesion Associated with Optic Nerve Invasion{triangledown} ,{dagger}

Nikia Laurie,1 Adithi Mohan,1 Justina McEvoy,1 Damon Reed,1 Jiakun Zhang,1 Brett Schweers,1 Itsuki Ajioka,1 Virginia Valentine,2 Dianna Johnson,3 David Ellison,4 and Michael A. Dyer1,3*

Departments of Developmental Neurobiology,1 Genetics and Tumor Cell Biology,2 Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,4 Department of Ophthalmology, University of Tennessee Health Sciences Center, Memphis, Tennessee 381053

Received 23 March 2009/ Returned for modification 9 May 2009/ Accepted 29 August 2009

In the 1970s, several human retinoblastoma cell lines were developed from cultures of primary tumors. As the human retinoblastoma cell lines were established in culture, growth properties and changes in cell adhesion were described. Those changes correlated with the ability of the human retinoblastoma cell lines to invade the optic nerve and metastasize in orthotopic xenograft studies. However, the mechanisms that underlie these changes were not determined. We used the recently developed knockout mouse models of retinoblastoma to begin to characterize the molecular, cellular, and genetic changes associated with retinoblastoma tumor progression and optic nerve invasion. Here we report the isolation and characterization of the first mouse retinoblastoma cell lines with targeted deletions of the Rb family. Our detailed analysis of these cells as they were propagated in culture from the primary tumor shows that changes in cadherin-mediated cell adhesion are associated with retinoblastoma invasion of the optic nerve prior to metastasis. In addition, the same changes in cadherin-mediated cell adhesion correlate with the invasive properties of the human retinoblastoma cell lines isolated decades ago, providing a molecular mechanism for these earlier observations. Most importantly, our studies are in agreement with genetic studies on human retinoblastomas, suggesting that changes in this pathway are involved in tumor progression.

* Corresponding author. Mailing address: Department of Developmental Neurobiology, MS 323, 262 Danny Thomas Place, St. Jude Children's Research Hospital, Memphis, TN 38105. Phone: (901) 595-2257. Fax: (901) 595-3143. E-mail: michael.dyer{at}stjude.org

{triangledown} Published ahead of print on 28 September 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, December 2009, p. 6268-6282, Vol. 29, No. 23
0270-7306/09/$08.00+0     doi:10.1128/MCB.00374-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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