Effects of recombinant human granulocyte colony-stimulating factor on the growth potential of two murine myeloid leukemias.
We investigated the in vitro and in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the proliferation of two murine leukemic cell lines. The rhG-CSF stimulated leukemic colony formation of the promyelocytic leukemic cell line L-8801 in methylcellulose culture and increased the number of L-8801 cells in liquid culture. However, rhG-CSF treatment prolonged the median survival period of mice implanted with L-8801 cells and the emergence of the leukemic blast cells in peripheral blood. Meanwhile, rhG-CSF had no influence on that of the megakaryoblastic leukemic cells L-8057 and failed to prolong the median survival period of L-8057 leukemic mice. Receptor binding analysis revealed that L-8801 cells expressed a G-CSF receptor (Kd=125 pM, 479 binding sites/cell) and L-8057 cells had no G-CSF receptors. Then, we examined the growth potential of these cells. The median survival period was longer for mice implanted with L-8801 cells cultured with rhG-CSF for 72 h in vitro than for cells grown without rhG-CSF. Furthermore, the median survival period of mice implanted with spleen cells from L-8801 leukemic mice treated with rhG-CSF was prolonged compared with those from leukemic mice without rhG-CSF. In contrast, there was no effect of rhG-CSF on the growth potential of the spleen from L-8057 leukemic mice. The results of our present study demonstrate that rhG-CSF reduced the growth of L-8801 leukemic cells in vitro and in vivo mediated through G-CSF receptors, thereby suppressing the development of leukemia.
Kabaya
K
K
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Gunma, Japan.
Obuchi
M
M
Kuwaki
T
T
Shibuya
K
K
Watanabe
M
M
Nemoto
K
K
Yoshida
K
K
Kusaka
M
M
Inoue
T
T
Seki
M
M
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor