St. Jude Identifies The Specific Cell That Causes Eye Cancer, Disproving Long-Held Theory

Investigators at St.
Jude Children's Research Hospital have identified the cell that gives rise
to the eye cancer retinoblastoma, disproving a long standing principle of
nerve growth and development. The finding suggests for the first time that
it may one day be possible for scientists to induce fully developed neurons
to multiply and coax the injured brain to repair itself.



A report of this work appears in the Oct. 19 issue of the journal
"Cell." Michael Dyer, Ph.D., an associate member in the St. Jude Department
of Developmental Neurobiology, is the report's senior author.



The immediate importance of the St. Jude finding is that it
unexpectedly showed that retinoblastoma can arise from fully matured nerves
in the retina called horizontal interneurons. This disproves the scientific
principle that fully formed, mature nerves cannot multiply like young,
immature cells, Dyer said. Human neurodegenerative disorders such as
Alzheimer's disease can occur when differentiated nerves in the brain try
to multiply, and in the process, trigger a self-destruct program called
apoptosis. Differentiation is the process by which cells lose their
primitive, stem-cell-like properties that include the ability to grow and
multiply, and instead develop specialized shapes and functions.



The St. Jude researchers showed that when the activity of the Rb family
of genes was reduced in the retina of mouse models, fully differentiated
horizontal neurons could multiply and yet retain all of the differentiated
features of normal horizontal neurons including neurites and synapses.



"For the past 100 years, it's been ingrained among scientists that
differentiated mature nerves are so elaborate that they can't divide, and
if they try to divide, they undergo cell death," Dyer said. "This is the
first time that anyone has shown that under certain conditions, a fully
mature and differentiated nerve can undergo cell division and multiply."




The discovery that fully differentiated horizontal interneurons can
multiply to form retinoblastoma also challenges the established scientific
belief that cancer cells are most aggressive when they are
undifferentiated, Dyer said. For example, the leukemic cells of chronic
myelogeneous leukemia (CML) are much less aggressive when they are
differentiated; and it is generally not aggressive until the tumor cells
sustain mutations that block differentiation.



An important implication of this finding is that if researchers were
able to alter the activity of certain genes in fully developed neurons,
they might be able to trigger them to multiply temporarily and replace the
neighboring neurons that were lost as a result of neurodegenerative
diseases such as Alzheimer's, Dyer said. "Having nerves duplicate
themselves might be more efficient than trying to stimulate nerve
replacement by inserting stem cells into the brain, since the existing
nerves would already be in the right place to restore missing brain cells,"
he said. "However, there is still a lot of research required to determine
if it is possible to control gene activity to make this approach
practical."



Other authors of this paper include Itsuki Ajioka, Rodrigo A. P.
Martins, Ildar T. Bayazitov, Stacy Donovan, Samantha Cicero, Kelli Boyd and
Stanislav S. Zakharenko (St. Jude); Dianna A. Johnson (University of
Tennessee Health Science Center, Memphis) and Sharon Frase (University of
Memphis).



This work was supported in part by the National Institutes of Health,
the National Cancer Institute, the American Cancer Society, Research to
Prevent Blindness, Pearle Vision Foundation, the International Retinal
Research Foundation, the Whitehall Foundation, NARSAD (The Mental Health
Research Association) and ALSAC. Dyer is a Pew Scholar; Zakharenko is a
Searle Scholar.



St. Jude Children's Research Hospital



St. Jude Children's Research Hospital is internationally recognized for
its pioneering work in finding cures and saving children with cancer and
other catastrophic diseases. Founded by late entertainer Danny Thomas and
based in Memphis, Tenn., St. Jude freely shares its discoveries with
scientific and medical communities around the world. No family ever pays
for treatments not covered by insurance, and families without insurance are
never asked to pay. St. Jude is financially supported by ALSAC, its
fundraising organization. For more information, please visit
stjude.


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