Neuroblastoma is a pediatric tumor of the sympatoadrenal lineage of the neural
crest characterized by high molecular and clinical heterogeneity, which are the main
causes of the poor response to standard multimodal therapy. The identification of new
and selective biomarkers is important to improve our knowledge on the mechanisms
of neuroblastoma progression and to find the targets for innovative cancer therapies.
This study identifies a positive correlation among tropomodulins (TMODs) proteins
expression and neuroblastoma progression. TMODs bind the pointed end of actin
filaments, regulate polymerization and depolymerization processes modifying actin
cytoskeletal dynamic and influencing neuronal development processes. Expression
levels of TMODs genes were analyzed in 17 datasets comprising different types
of tumors, including neuroblastoma, and it was demonstrated that high levels of
tropomodulin1 (TMOD1) and tropomodulin 2 (TMOD2) correlate positively with
high survival probability and with favorable clinical and molecular characteristics.
Functional studies on neuroblastoma cell lines, showed that TMOD1 knockin induced
cell cycle arrest, cell proliferation arrest and a mature functional differentiation.
TMOD1 overexpression was responsible for particular cell morphology and biochemical
changes which directed cells towards a neuronal favorable differentiation profile.
TMOD1 downregulation also induced cell proliferation arrest but caused the loss of
mature cell differentiation and promoted the development of neuroendocrine cellular
characteristics, delineating an aggressive and unfavorable tumor behavior. Overall,
these data indicated that TMODs are favorable prognostic biomarkers in neuroblastoma
and we believe that they could contribute to unravel a new pathophysiological
mechanism of neuroblastoma resistance contributing to the design of personalized
therapeutics opportunities
