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)‐α and interleukin (IL)‐1β 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)‐κB 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.