title: Effect of serum deprivation on constitutive production of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells.
abstract: We previously established 2 lung cancer cell lines, OKa-C-1 and MI-4, which constitutively produce an abundant dose of granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF). Many other cases with G-CSF or GM-CSF producing tumors have been reported up to the present. However, the biological properties of the overproduction of G-CSF and GM-CSF by tumor cells have not been well known. Several reports demonstrated the presence of an autocrine growth loop for G-CSF and GM-CSF in nonhematopoietic tumor cells. We showed that exogenous G-CSF and GM-CSF stimulated cell growth in a dose-dependent manner in OKa-C-1 and MI-4 cells. We could detect the presence of G-CSF and GM-CSF receptors in both cell lines by RT-PCR analysis. We have previously shown that inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta enhance the expression of G-CSF and GM-CSF in the cell lines. However, the factors that regulate constitutive production of G-CSF or GM-CSF by tumor cells are still unknown well. In our study, we first reported that serum deprivation stimulated constitutive production of G-CSF and GM-CSF by lung tumor cells through activation of nuclear factor (NF)-kappaB and p44/42 mitogen-activated protein kinase (MAPK) pathway signaling. We suggest that G-CSF and GM-CSF constitutively produced by tumor cells could grow tumor itself and rescue tumor cells from the cytotoxicity of serum deprivation.
authors.affiliation: Department of Internal Medicine, Kochi Medical School, Kohasu, Okocho, Nankoku, Kochi, Japan. uemuray@kochi-ms.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Uemura
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hideshi
authors.initials: H
authors.lastname: Nakata
authors.forename: Ryoji
authors.initials: R
authors.lastname: Harada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kubota
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Taguchi
mesh_terms: D018287:Carcinoma, Large Cell / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D016895:Culture Media, Serum-Free; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases