Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression

Kamohara, Hidenobu; Ogawa, Michio; Ishiko, Takatoshi; Saito, Kiyoshi; Baba, Hideo

doi:10.3892/ijo.30.4.977

Cited by 44 publications

(56 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In many cell types, exogenous LIF upregulates LIFR mRNA expression [81,82]. In contrast, we observed that in response to LIF stimulation in NP cells, LIFR expression remained unchanged, but gp130 mRNA was upregulated in a concentration-dependent fashion (Fig.…”

Section: Signaling Pathways Activated By Lifcontrasting

confidence: 43%

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

et al. 2012

View full text Add to dashboard Cite

Various growth factor cocktails have been used to proliferate and then differentiate human neural progenitor (NP) cells derived from embryonic stem cells (ESC) for in vitro and in vivo studies. However, the cytokine leukemia inhibitory factor (LIF) has been largely overlooked. Here, we demonstrate that LIF significantly enhanced in vitro survival and promoted differentiation of human ESC-derived NP cells. In NP cells, as well as NP-derived neurons, LIF reduced caspase-mediated apoptosis and reduced both spontaneous and H 2 O 2 -induced reactive oxygen species in culture. In vitro, NP cell proliferation and the yield of differentiated neurons were significantly higher in the presence of LIF. In NP cells, LIF enhanced cMyc phosphorylation, commonly associated with self-renewal/proliferation. Also, in differentiating NP cells LIF activated the phosphoinositide 3-kinase and signal transducer and activator of transcription 3 pathways, associated with cell survival and reduced apoptosis. When differentiated in LIF 1 media, neurite outgrowth and ERK1/2 phosphorylation were potentiated together with increased expression of gp130, a component of the LIF receptor complex. NP cells, pretreated in vitro with LIF, were effective in reducing infarct volume in a model of focal ischemic stroke but LIF did not lead to significantly improved initial NP cell survival over nontreated NP cells. Our results show that LIF signaling significantly promotes human NP cell proliferation, survival, and differentiation in vitro. Activated LIF signaling should be considered in cell culture expansion systems for future human NP cell-based therapeutic transplant studies.

show abstract

Section: Signaling Pathways Activated By Lifcontrasting

confidence: 43%

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Apoptotic activity of TNF-α is dominant via receptor containing death domain, particularly 55-kDa TNF receptor (TNFRI), despite the strong inducer of CXCL-8. Our previous reports demonstrated that exogenous LIF promoted cell growth by the mechanisms upregulating endogenous LIF and LIFR expression in Hs-700T cells which produced a small amount of LIF (8,20). In this study, LIF induced expression of CXCL-8 transcript at levels that were limited in comparison with TNF-α.…”

Section: Discussionmentioning

confidence: 73%

Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-α and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor

Kamohara

Takahashi²,

Ishiko³

et al. 2007

Int J Oncol

Self Cite

View full text Add to dashboard Cite

Abstract. Pancreatic carcinoma is one of the most lethal of the gastrointestinal malignant tumors. Chronic inflammation leads to cancer development and progression. Interleukin-8 (CXCL-8) is a CXC chemokine, which plays an important role in neutrophil chemotaxis and activation. We previously reported that CXCL-8 was produced by a variety of human carcinoma cells and tissues, and that CXCL-8 promoted proliferation in pancreatic carcinoma cells (SUIT-2). In the present study, we analyzed whether various cytokines affect cell proliferation by CXCL-8 expression in pancreas carcinoma cells. All examined pancreatic carcinoma cells expressed CXCL-8 and TNFRII mRNA constitutively in RPMI-1640 medium without FBS. TNF-α, LIF, IL-1ß, IL-6, IL-8, or IFN-ß enhanced the expression of CXCL-8 mRNA, but IL-10 did not in Hs-700T cells. Actinomycin D suppressed and cycloheximide augmented CXCL-8 mRNA which was induced by TNF-α or not. The half-life of CXCL-8 mRNA was 36.5 min by TNF-α and 35.2 min by no stimulation. In our previous study, LIF promoted cell growth in Hs-700T cells. LIF induced CXCL-8 mRNA in a dose-and time-dependent manner. Addition of recombinant CXCL-8 did not induce cell growth of Hs-700T. Anti-CXCL-8 IgG significantly suppressed cell growth. CXCL-8 would act as an autocrine growth factor in Hs-700T cells, which expressed CXCL-8 mRNA highly without stimulation. Curcumin (diferuloylmethane), NF-κB inhibitor, suppressed cell proliferation in Hs-700T cells. These results suggest that CXCL-8 plays a pivotal role in progression of pancreatic cancer, and its expression is influenced by inflammatory cytokines in pancreatic tumor microenvironment.

show abstract

“…Among them, only LIF-mediated STAT3 signaling has been defined in detail. Recently, dysregulation of LIF and/or the LIF receptor (LIFR) has been reported in several human malignancies, including glioblastoma (21), thyroid cancer (22), rhabdomyosarcoma (23), pancreatic carcinoma (24,25), and breast cancer (26). However, the precise role of LIF in tumorigenesis remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance

Liu¹,

et al. 2013

View full text Add to dashboard Cite

Radioresistance of EBV-associated nasopharyngeal carcinoma (NPC) is associated with poor prognosis for patients with this form of cancer. Here, we found that NPC patients had increased serum levels of leukemia inhibitory factor (LIF) and that higher LIF levels correlated with local tumor recurrence. Furthermore, in vitro studies with NPC cells and in vivo xenograft mouse studies demonstrated that LIF critically contributes to NPC tumor growth and radioresistance. Using these model systems, we found that LIF treatment activated the mTORC1/p70S6K signaling pathway, enhanced tumor growth, inhibited DNA damage responses, and enhanced radioresistance. Treatment with either soluble LIF receptor (sLIFR), a LIF antagonist, or the mTOR inhibitor rapamycin reversed LIF-mediated effects, resulting in growth arrest and increased sensitivity to γ irradiation. Immunohistochemical (IHC) analyses of human NPC biopsies revealed that LIF and LIFR were overexpressed in tumor cells and that LIF expression correlated with the presence of the activated p-p70S6K. Finally, we found that the EBV-encoded protein latent membrane protein 1 (LMP1) enhances LIF production. Together, our findings indicate that LIF promotes NPC tumorigenesis and suggest that serum LIF levels may predict local recurrence and radiosensitivity in NPC patients.

show abstract

Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression

Cited by 44 publications

References 23 publications

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-α and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor

Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance

Contact Info

Product

Resources

About