We investigated secretion of hematopoietic growth factors in ten human tumor cell lines, derived from 5 different tissue types. The cell lines were stimulated transiently with interleukin-1 (IL-1 ), IL-6, interferon-ç (IFN-ç), lipopolysaccharide (LPS) and tetradecanoyl phorbol 13-acetate (TPA), respectively. Conditioned media (CM) were screened in a bioassay using an indicator cell line which is growth factor-dependent and needs the supply of at least one hematopoietic cytokine. The CM of almost all tumor cell lines analyzed induced proliferation of this indicator cell line as documented by incorporation of [3H]-thymidine. The majority of constitutively cytokine-producing tumor cell lines could be induced to further increase their amounts of secreted proliferation-inducing activity. The strongest inducers were TPA and IL-1 ; weakly or not effective at all were IFN-ç, LPS and IL-6. Enzyme-linked immunosorbent assay (ELISA) identified several cytokines and macrophage-colony-stimulating factor (M-CSF) and IL-6 were secreted at the highest concentrations. Especially in kidney cell lines, the levels of granulocyte-macrophage-CSF (GM-CSF), M-CSF and IL-6 were further strongly increased by the TPA and IL-1 pretreatment. The by far highest amounts of granulocyte-CSF (G-CSF) were elaborated by the bladder cell line T-24 and could be further more than doubled by TPA. Other cell lines, derived from esophagus, lung and pancreas, responded less strongly to the pretreatment with the biomodulators. Our results demonstrating secretion of functionally active cytokines by human solid tumor cell lines suggest that these, to date so-called, hematopoietic cytokines are not entirely hematopoietic specific and might play a fundamentally important role in tumor cell biology.

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