Cancer cell lines' growth is promoted through individual responsiveness to autocrine and/or exogeneous erythropoietin in vitro

摘要

Erythropoietin (Epo) therapy for combatting anemia or fatigue in cancer patients has become a controversial issue. We have previously reported our study of 24 malignant human cell lines which express Epo and its receptor (EpoR) mRNAs and secrete Epo protein; blockade of Epo-signal destroyed the xenografts of female malignancies [1] and cancer cell lines [2]. We speculated that the conflicting clinical outcomes are due to the individual responsiveness to Epo of the various cancers. We measured the expression levels of Epo and EpoR mRNAs and the amount of Epo protein secreted and demonstrated the presence of EpoR protein in these 24 cell lines, some of which had anoxia-inducible Epo and/or EpoR mRNA. Additionally in seven selected cell lines with known amounts of Epo and EpoR expression, rhEpo triggered and the EpoR antagonist (EMP9) inhibited tyrosine phosphorylation of STAT5. They showed a rhEpo-induced growth that corresponded generally to the level of the constitutive activation of tyrosine phosphorylation of STAT5. Further, EMP9-suppressed growth depended inversely on the amount of Epo secretion. These data justify our speculation that the growth of very many cancers is promoted by their own Epo-signal which may or may not be accelerated by exogenous rhEpo.