NON-TELEOLOGICAL DIFFERENTIATION OF MALIGNANCY (REVIEW)

So-called 'de-differentiation' of malignant tumors is not identical with 'retro-differentiation' of normal cells, although induction of differentiation of tumor cells seems to be successful. De-differentiation of tumor cells is a more stochastic process than the reversion of serial developmental lineage in normal differentiation. After retro-differentiation, re-differentiation of normal cells includes serial expression of negative regulators programmed a priori, and a teleological explanation of differentiation is possible. However, 'fragmented' gene expression is generally observed in tumor-cell differentiation. In tumor cells, it is more important that they cannot maintain a differentiated state under normal microenvironments than that they can be induced to differentiate by artificial agents. Induction of differentiation of tumor cells should be different from that of their normal counterparts since loss of regulatory mechanisms could not be restored by the inducers. Phenomenological homology between tumor cells and their normal counterparts in the differentiation may be only an experimental artifact, since the genetic information of development is generally damaged or lost in tumor cells. Loss of teleology in tumor cells is essentially correlated with their selfish behavior. Differentiation is not necessary for tumor cells, since they are 'selfish cells' in the altruistic somatic cell society. The differentiation program of tumor cells should be considered as a remnant of the normal one with loss of teleology.