Clonal heterogeneity of a human functioning tumor which produces granulocyte colony-stimulating factor

Two different clonal strains have been isolated from a human squamous cell carcinoma which produces granulocyte colony-stimulating factor (G-CSF). The clones differed in morphology, growth characteristics, karyotype, production of G-CSF, histology of the tumors produced by inoculating the cultured cells, and in the development of granulocytosis in host mice transplanted with the cultured cells. A well-differentiated squamous cell carcinoma was developed by inoculation with clone 1 cells into athymic nude mice. No CSF activity was detected in the cultured medium of the cells. The host mice with the transplanted cells showed no increase in peripheral blood neutrophils. Clone 2, which formed a poorly-differentiated squamous cell carcinoma in nude mice, produced a large amount of CSF in vitro and developed a marked neutrophilia in host nude mice. Clone 1 cells were more sensitive to bleomycin than were clone 2 cells in vitro. The results suggested the G-CSF producing tumor to be heterologous and the cells with different functional properties, including G-CSF production, sensitivity to bleomycin, and keratinization, to pre-exist in the parental cell population.