STIMULATION OF MEGAKARYOCYTOPOIESIS DURING EXPERIMENTAL TUMOR-GROWTH IN MICE

Background - In an attempt to elucidate the mechanism of tumor-associated stimulated thrombopoiesis, the effect of Sarcoma 180 (S180) ascites tumor growth on host megakaryocytopoiesis has been investigated in Swiss mice. Methods - Megakaryocyte (MK) progenitor cells - CFU-MK and MK CFU-S were assayed in vitro in soft agar and in vivo in spleens of lethally-irradiated mice respectively. Immature megakaryocytes were identified as small acetylcholinesterase-positive cells with a diameter of < 13-mu-m while the mature cells are < 13-mu-m in diameter. Results - CFU-MK population was increased by 1.7-fold and 3-fold over control values in the femoral marrow and spleen respectively at the early phase of tumor growth (day 5 post-transplantation). Further enhancement was observed particularly in the spleen during the log phase (between day 7 and day 10) of tumor progression. S180 cell conditioned medium also stimulated CFU-MK colony growth in vitro. The number of MK CFU-S, considered more primitive than CFU-MK, was also enhanced significantly (P < 0.05) particularly during the period of intense tumor growth. The numbers of both mature and immature MKs were elevated modestly in the bone marrow but remarkably in the spleeen (P < 0.01) throughout the period of tumor growth. Conclusions - The results indicated that accelerated thrombopoiesis in S180-bearing mice may be the consequence of stimulation at the level of primitive as well as committed MK progenitor cells especially in the spleen, and S180 tumor cells possibly produce substance(s) that have growth promoting activity for MK progenitors.