Circadian synchronization of cell proliferation is observed not only in normal healthy tissues but also in malignant solid
tumors. However, the proliferation rhythm of
tumor cells is often different from that of normal cells. We reported here that the peculiar rhythm of
tumor cell proliferation was modulated by inhibition of
platelet-derived growth factor (PDGF) signaling.
DNA synthesis in
tumor cells implanted in mice showed a 24-h oscillation apparently differing from that of normal bone marrow cells. Continuous administration of
AG1295 (10 microg/h, s.c.), a
PDGF receptor tyrosine kinase inhibitor, substantially suppressed
DNA synthesis in the implanted
tumor cells but not in the healthy bone marrow cells. During the administration of this
drug, the rhythm of
DNA synthesis in the
tumor cells was synchronized with that in bone marrow cells. The present results suggest that the circadian rhythm of
DNA synthesis in
tumor cells is modulated by
PDGF receptor signaling, which is activated following
tumor progression. Because the rhythmic patterns of clock gene expression in
tumor cells did not differ significantly from those in other healthy tissues, the enhanced signal transduction of
PDGF receptor may cause an alteration in the rhythmicity of
tumor cell proliferation without changing in the intracellular molecular clockwork.