Activity of growth factors in the IL-6 group in the differentiation of human lung adenocarcinoma

Abstract

The role of the interleukin-6 (IL-6) group of cytokines in differentiation of two lung adenocarcinoma cell lines has been examined using induction of alkaline phosphatase and expression of surfactant protein A. Oncostatin M was the most active and potent for alkaline phosphatase in A549 cells, with IL-6 having similar activity but less potency. Neither cytokine induced alkaline phosphatase in NCI-H441 cells, although induction was obtained with lung fibroblast-conditioned medium. Surfactant protein A was induced in NCI-H441 cells by conditioned medium and dexamethasone and, to a much lesser extent, by oncostatin M or IL-6. Induction of alkaline phosphatase and surfactant protein A were both dexamethasone-dependent, though some induction of surfactant protein A was obtained with interferon-α in the absence of dexamethasone. The activity present in lung fibroblast-conditioned medium suggests paracrine control, but this appears not to be due to oncostatin M or IL-6 as disabling antibodies to either cytokine were not inhibitory, and, although alkaline phosphatase was induced in A549 by both cytokines, it was only induced by conditioned medium in NCI-H441 cells. Furthermore, surfactant protein A was induced in H441 by conditioned medium to a much greater extent than by oncostatin M or IL-6. These data demonstrate that cytokines of the IL-6 group have potential as differentiation inducers in lung adenocarcinoma cells and that there is an equivalent paracrine factor(s) in lung fibroblast conditioned medium. As the production of this factor by fibroblasts is not enhanced by glucocorticoid, although the response of the target cell is, it would appear to be distinct from the fibrocyte pneumocyte factor previously described by Post et al 1984 Nature 308 : 284–286. © 2000 Cancer Research Campaign

Overexpression of Oncoprotein 18 Correlates with Poor Differentiation in Lung Adenocarcinomas

“…Op18b was not analyzed due to its low abundance in these cell lines and thus the difficulty of quantification on 2D gels. To further verify this result, we compared the changes in Op18 expression after treatment with DX, DX ϩ IL-6, or DX ϩ IFN-␣, which are reported to induce cell differentiation (31,32). Op18 was decreased following DX ϩ IL-6 treatment for 24 -72 h as compared with controls (0 h) in both A549 and SKLU1 cell lines.…”

“…Cell differentiation in lung cells can be induced by treatment with DX, IL-6, or IFN-␣ (31,32). Higher levels of Op18 were found in the poorly differentiated SKLU1 cells as compared with the well differentiated A549 cells.…”

Inhibition of Growth and Induction of Differentiation of SMMC-7721 Human Hepatocellular Carcinoma Cells by Oncostatin M

“…Among those cytokines, the highest activity and greatest potency of inducing differentiation was found with OSM. Activities may be ranked as follows: OSM > IL-6 > LIF > IL-11 > G-CSF > CNTF (McCormick and Freshney, 2000).…”

“…Roles of OSM in adult liver include regeneration, tissue remodeling (Okaya et al, 2005), regulating lipid metabolism (Kong et al, 2005), preventing hepatocytes apoptosis, prevention and treatment of liver injury (Hamada et al, 2007). There has been previously reported that OSM can induce morphology and/or function differentiation and maturation of many tumor cells, which are as follows: glioma cells (Chen et al, 2006), glioblastoma cells (Halfter et al, 2006), osteosarcoma cells (Brounais et al, 2009), breast cancer cells (West et al, 2012), lung adenocarcinoma cells (McCormick and Freshney, 2000), myeloid leukemia cells (Bruce et al, 1992). OSM can induce cells to differentiate into hepatocytes from embryonic stem cells (ES cells) (Hay et al, 2008), bone marrow-derived mesenchymal stem cells (Wei et al, 2008), umbilical cord blood-derived mesenchymal stem cells (Sensken et al, 2007), adipose tissue-derived stromal cells (hADSC) and hepatic stem cells in liver with cooperative effects of HGF (Kamiya et al, 2006).…”

IL-6-transfected tumor cells modulate the status of CD8+ and CD4+ T cells to control tumor growth

“…However, the effect of IL-6 on cancer development is not straightforward. For example, IL-6 has the potential to act as an inducer of differentiation in lung adenocarcinoma cells (McCormick and Freshney 2000;McCormick et al 1995) or as a growth factor for breast (Sasser et al 2007;Studebaker et al 2008) and prostate cancer (Okamoto et al 1997). There is evidence of constitutive IL-6 production in various cancer cells (Van Meir et al 1990;Watson et al 1990;Yamaji et al 2004) and it is thought IL-6 acts not only on the tumor but also the immune system.…”