Effects of GM-CSF and M-CSF on tumor progression of lung cancer: Roles of MEK1/ERK and AKT/PKB pathways

Uemura, Yoshiki; Nakata, Hideshi; Kubota, Tetsuya; Bandobashi, Kentaro; Saito, Tsuyako; Taguchi, Hirokuni

doi:10.3892/ijmm.18.2.365

Cited by 31 publications

(28 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, GM-CSF production by breast cancer cells was suggested to enhance tumor growth and to promote the formation of bone metastases, possibly by stimulating resident macrophages or by inducing osteoclast differentiation and activation (33). Lung cancer cells have also been shown to produce GM-CSF and their proliferation may be enhanced by exogenous GM-CSF (34).…”

Section: Discussionmentioning

confidence: 99%

GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer

Nebiker

Han

Eppenberger‐Castori

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF-and M-CSF-specific antibodies. Clinicopathological features and overall survival were analyzed.Results: GM-CSF induced CD16 expression in 66% AE 8% of monocytes, as compared with 28% AE 1% in cells stimulated by M-CSF (P ¼ 0.011). GM-CSF but not M-CSF-stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n ¼ 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1b and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P ¼ 0.02), "pushing" growth pattern (P ¼ 0.004) and significantly (P ¼ 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16 þ and CD8 þ cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance. Conclusions: GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer. Clin Cancer Res; 20(12); 3094-106. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer

Nebiker

Han

Eppenberger‐Castori

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…IL-12 or molecules like NOS-2 or SerpinF1, which are expressed under the control of NF-κB. Interestingly, IL-6, IL-8, CSF-2 (GM-CSF), and NOS-2 have been implicated in survival or proliferation of tumor cells (53)(54)(55)(56)(57)(58). Upregulation of KDR (VEGFR2) and downregulation of SerpinC1 were observed after TLR7 or TLR8 stimulation.…”

Section: Figurementioning

confidence: 99%

Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance

Cherfils‐Vicini¹,

Platonova²,

Gillard³

et al. 2010

J. Clin. Invest.

200

178

View full text Add to dashboard Cite

Compelling evidence suggests that inflammation, cell survival, and cancer are linked, with a central role played by NF-κB. Recent studies implicate some TLRs in tumor development based on their ability to facilitate tumor growth; however, to our knowledge, involvement of neither TLR7 nor TLR78 has yet been demonstrated. Here we have demonstrated expression of TLR7 and TLR8, the natural receptors for single-stranded RNA, by tumor cells in human lung cancer in situ and in human lung tumor cell lines. Stimulation with TLR7 or TLR8 agonists led to activated NF-κB, upregulated expression of the antiapoptotic protein Bcl-2, increased tumor cell survival, and chemoresistance. Transcriptional analysis performed on human primary lung tumor cells and TLR7-or TLR8-stimulated human lung tumor cell lines revealed a gene expression signature suggestive of chronic stimulation of tumor cells by TLR ligands in situ. Together, these data emphasize that TLR signaling can directly favor tumor development and further suggest that researchers developing anticancer immunotherapy using TLR7 or TLR8 agonists as adjuvants should take into account the expression of these TLRs in lung tumor cells.

show abstract

“…For example, CD14+ cells, which typically mark monocyte/macrophages, give rise to osteoblasts, skeletal myoblasts, chondrocytes, and adipocytes (28,37,77,126,145,147). Thus, inflammatory cells may participate in lung repair/remodeling in classic and nonclassic pathways.…”

Section: Plasticity Hypothesismentioning

confidence: 99%

The Role of Inflammation in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Bringardner

Baran

Eubank

et al. 2008

Antioxidants & Redox Signaling

256

190

View full text Add to dashboard Cite

The role of inflammation in idiopathic pulmonary fibrosis (IPF) is controversial. If inflammation were critical to the disease process, lung pathology would demonstrate an influx of inflammatory cells, and that the disease would respond to immunosuppression. Neither is true. The classic pathology does not display substantial inflammation, and no modulation of the immune system is effective as treatment. Recent data suggest that the pathophysiology of the disease is more a product of fibroblast dysfunction than of dysregulated inflammation. The role of inflammation in disease pathogenesis comes from pathology from atypical patients, biologic samples procured during exacerbations of the disease, and careful examination of biologic specimens from patients with stable disease. We suggest that inflammation is indeed a critical factor in IPF and propose five potential nontraditional mechanisms for the role of inflammation in the pathogenesis of IPF: the direct inflammatory hypothesis, the matrix hypothesis, the growth factor-receptor hypothesis, the plasticity hypothesis, and the vascular hypothesis. To address these, we review the literature exploring the differences in pathology, prognosis, and clinical course, as well as the role of cytokines, growth factors, and other mediators of inflammation, and last, the role of matrix and vascular supply in patients with IPF.

show abstract

Effects of GM-CSF and M-CSF on tumor progression of lung cancer: Roles of MEK1/ERK and AKT/PKB pathways

Cited by 31 publications

References 23 publications

GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer

GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer

Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance

The Role of Inflammation in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Contact Info

Product

Resources

About