Alternative production of Bcl-2 and Bax by tumor cells determines the rates of in vivo tumor progression: suggested mechanisms.

The hypothesis tested in the study suggests that mechanisms of the earlier described delayed or accelerated tumor progression may be regulated by the antiapoptotic and proapoptotic cellular programs activated in stress reactions of transformed cells to the host normal cellular environment. Therefore, spontaneously transformed hamster cell line STHE, its bcl-2-transduced line STHE-Bcl-2, and 64 of their descendant tumor cell variants naturally selected in two in vivo regimes (local tumor growth versus dissemination) were examined. The role of Bcl-2 and the possible activation of endogenous death-signaling Bax, Ras, and HSP90/HSP70 stress proteins in STHE (Bcl-2+/-) tumor cell variants were studied in dynamics of in vivo tumor progression.

The fingerprints of the host innate immunity on the cells of primary virus-induced tumors.

As shown earlier, the cells transformed in vitro by various oncogenes, during subsequent in vivo growth were gradually replaced by descendant tumor cells, which co-expressed highly increased H(2)O(2)-catabolizing antioxidant activity (H(2)O(2)(CA)), and the ability to release PGE(2) (PGE(S)) in contact with natural killer cells; v-src was the only oncogene, which in vitro induced cells transformation characterised with the expression of [H(2)O(2)(CA)+PGE(S)] phenotype. Expression of [H(2)O(2)(CA)+PGE(S)] phenotype was providing tumor cells with significantly increased resistance to cytotoxic activities of macrophages and NK cells. However, the possible involvement of [H(2)O(2)(CA)+PGE(S)] phenotype in primary carcinogenesis remained obscure.

In vivo acquired mechanisms of tumor cells local defense against the host innate immunity effectors: implication in specific antitumor immunity.

As shown earlier, the cells transformed in vitro by several different oncogenes, or spontaneously, during in vivo growth in normal hosts would be gradually replaced by the highly-tumorigenic descendants co-expressing high H2O2-catabolizing and PGE2-releasing activities. Acquisition of (H2O2(CA) + PGE(S)) phenotype provides the cells with local defense mechanisms against the host innate immunity effectors. However, it remained unknown, whether the expression of (H2O2(CA) + PGE(S)) phenotype is implicated in susceptibility of tumor cells expressing tumor-specific transplantation antigens to rejection in immune animals.