Die Bedeutung der Hedgehog- Signalkaskade in der Tumorgenese von spinalen und kraniellen Chordomen

Abstract

Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine, arising from remnants of embryonic notochord. Although they are slow growing, chordomas are highly recurrent, locally invasive and aggressive. Since chordomas arise in bone, they are usually extradural and result in local bone destruction. The prognosis of chordoma patients remains poorly. Radical surgery and high- dose radiation are the most useful treatment. Traditional chemotherapy has not been shown to be effective. Chordomas are complicated tumors to treat due to the involvement of critical structures such as the brainstem, spinal cord, and important nerves and arteries. Understanding the intracellular mechanisms of chordoma formation may help to develop an appropriate chemotherapeutic agent. The hedgehog pathway regulates multiple processes involved in development and differentiation of tissues and organs during embryonic life, as well as cell growth and differentiation in the adult organism, where the aberrant activation has been implicated in several cancers. To explore the role of hedgehog signaling in skull base and sacrum chordomas, we detected immuno histochemically the expression of Shh and Gli1, as well as Ptch1 and Gli1 by in- situ- hybridization. We assume a canonical, ligand- dependent and autocrine hedgehog signaling in skull base and sacral chordomas and their recurrences. A paracrine or non-canonical pathway cannot be excluded certainly. We anticipate that inhibitors of hedgehog pathway, like Shh-, Gli- and Smo- inhibitors, may have a positive clinical therapeutically effects for the treatment of chordomas.