PATHOBIOLOGY OF THE RARITY OF EXTRACRANIAL METASTASES IN TUMORS OF THE CENTRAL-NERVOUS-SYSTEM

Primary tumors of the central nervous system (CNS) very rarely metasta size to other parts of the body, both in animals and in man, irrespect ive of survival time. The only exception to this rule is observed in m eningeomas in man with a metastasis incidence of 18.7%. Experimental s tudies have provided strong evidence for an important modulating role of the extracellular matrix upon the invasion capacity of tumors. Mali gnant progression of tumors depends upon accumulation of somatic mutat ions which impart a selective advantage for invasion into the surround ing connective stroma. Such mutations seem to result from an active co nfrontation and interaction between tumor cells and components of the stroma. As the parenchyme of the CNS is largely free of connective tis sue no such selection interplay occurs in genuine CNS tumors, in contr ast to tumors of the other parts of the body with an abundance of conn ective tissue surrounding them. This explains the rarity of extracrani al metastases of CNS tumors. Ln contrast, other tumors of the body met astasize more frequently into the CNS. Obviously, this potency is corr elated with the frequency of mutations at the CD44 gene locus.