Effect of serum deprivation on constitutive production of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells

Int J Cancer. 2004 May 10;109(6):826-32. doi: 10.1002/ijc.20023.

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.

MeSH terms

  • Carcinoma, Large Cell / metabolism*
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Division
  • Culture Media, Serum-Free
  • Granulocyte Colony-Stimulating Factor / biosynthesis*
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Humans
  • Interleukin-1 / pharmacology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Granulocyte Colony-Stimulating Factor / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Culture Media, Serum-Free
  • Interleukin-1
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases