Keratoepithelin in neuroblastoma: molecular mechanisms and functional studies

Neuroblastoma (NB) is the most common solid tumor of infancy. Approximately 40% of the affected children die in spite of aggressive multimodal therapy. The N-myc oncogene is probably causally involved in the progression of neuroblastomas but other factors may equally contribute.

We found that Activin-A expression in neuroblastoma is a favourable prognostic marker (1). Activin-A transfected NB cell lines lead to poorly vascularized tumors in orthotropic mouse model despite high N-myc levels. A particular mechanism by which activin-A may act in human neuroblastomas is the up regulation of Keratoepithelin. Using Affimetrix® gene chips arrays for expression profiling, we detected Keratoepithelin expression significantly increased in Activin-A-transfected NB cells compared to the parental cell line. Our recent studies indicate that Keratoepithelin may suppress neuroblastoma growth and progression by modulating distinct pathways involved in cell adhesion and migration as well as tumor angiogenesis.

1. Breit, S., Ashman, K., Wilting, J., Rössler, J., Hatzi, E., Fotsis, T. and Schweigerer, L. (2000) The N-myc Oncogene in Human Neuroblastoma Cells: Down Regulation of an Angiogenesis Inhibitor Identified as Activin A. Cancer Research 60: 4596–45601