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Establishment and Propagation of Human Retinoblastoma Tumors in Immune Deficient Mice
Published on: August 4, 2011
Changes in retinoblastoma cell adhesion associated with optic nerve invasion
Nikia Laurie1, Adithi Mohan, Justina McEvoy
1Department of Developmental Neurobiology, MS 323, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Molecular and Cellular Biology
|September 30, 2009
Summary
Researchers identified changes in cell adhesion as a key mechanism driving retinoblastoma (RB) tumor progression and optic nerve invasion. These findings in mouse models mirror earlier human studies, revealing a molecular basis for RB metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Human retinoblastoma cell lines established in the 1970s showed altered cell adhesion correlating with tumor invasion.
- The underlying molecular mechanisms for these changes remained undetermined.
- Recent advancements include the development of knockout mouse models for retinoblastoma.
Purpose of the Study:
- To characterize molecular, cellular, and genetic changes in retinoblastoma tumor progression and optic nerve invasion.
- To isolate and characterize the first mouse retinoblastoma cell lines with targeted deletions of the Rb family.
- To elucidate the molecular mechanisms of retinoblastoma invasion and metastasis.
Main Methods:
- Isolation and characterization of mouse retinoblastoma cell lines from knockout models with Rb family deletions.
- Propagation of cells in culture from primary tumors.
- Analysis of cadherin-mediated cell adhesion changes during tumor progression.
- Correlation of findings with human retinoblastoma cell line data and genetic studies.
Main Results:
- The first mouse retinoblastoma cell lines with targeted Rb family deletions were successfully isolated and characterized.
- Changes in cadherin-mediated cell adhesion were observed as cells were propagated in culture.
- These cadherin alterations correlated with retinoblastoma's ability to invade the optic nerve prior to metastasis.
- Similar cadherin changes were found in older human retinoblastoma cell lines, linking them to invasive properties.
Conclusions:
- Alterations in cadherin-mediated cell adhesion provide a molecular mechanism for retinoblastoma invasion of the optic nerve.
- These findings in mouse models validate and explain observations from early human retinoblastoma studies.
- The identified pathway involving cadherin changes is implicated in human retinoblastoma tumor progression, aligning with genetic studies.
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