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.