Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer

Shi, Jingwei; Song, Xuejing; Traub, Benno; Luxenhofer, Michael; Kornmann, Marko

doi:10.3390/ijms22062998

Cited by 51 publications

(50 citation statements)

References 139 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Involvement of different MMPs and IL4 and IL13 are known to be associated with progression of human PDAC. 50-52 Specifically, expression of KRAS and P53 was also found to be up regulated in the porcine pancreatic tumors (Fig. 6C).…”

Section: Resultsmentioning

confidence: 79%

“…50, 51, 53, 54 In addition, genes associated with IL4 and IL13 signaling were also found to be up regulated in OCM tumors, which are known to be a major component of tumor microenvironment (TME) and have significant contributions in progression and metastasis of several cancers including PDAC. 52, 59…”

Section: Resultsmentioning

confidence: 99%

“…50,51,53,54 In addition, genes associated with IL4 and IL13 signaling were also found to 27 be up regulated in OCM tumors, which are known to be a major component of tumor microenvironment (TME) and have significant contributions in progression and metastasis of several cancers including PDAC. 52,59 Taken together, it can be concluded that AdCre injection into the connecting lobe (method 2) of the transgenic swine model (LSL-KRAS G12D -IRES-TP53 R167H ) generated pancreatic cancer at a frequency of 75%. All had a similar terminal course: failure to thrive, which was secondary to gastric outlet obstruction, which was secondary to a peripancreatic phlegmon, which was secondary to pancreatitis, which appeared to be secondary to tumor.…”

Section: Porcine Pancreatic Tumors Express Known Genes and Pathways L...mentioning

confidence: 97%

See 2 more Smart Citations

Induction of pancreatic neoplasia in theKRAS/TP53Oncopig

Patel

Bailey

Lazenby

et al. 2020

Preprint

View full text Add to dashboard Cite

Introduction.Five-year survival (all patients) from pancreatic cancer (PC) is in the range of 10%, and has not changed substantially in decades. Current murine models may not adequately mimic human PC, and can be inadequate for device development, which all may contribute to the lack of progress in PC survival. We attempted PC induction in transgenic swine (expressing KRAS and TP53 mutants) with the ultimate goal of creating a more accurate model of PC.Methods. Transgenic Oncopigs (n = 16, malensrrc.missouri.edu; somatic LSL cassette with TP53 R167H and KRAS G12D ) were injected via laparotomy with AdCre (10 10 vp/mL) ± IL-8 (0.5-2 ng; a tumor induction adjunct facilitating adenoviral entry into epithelia and promoting local inflammation) into the main pancreatic duct (MPD; via duodenotomy) or duct to the isolated pancreatic connecting lobe (CL). Subjects were necropsied after ≤10 wk, followed by histology.

show abstract

Section: Resultsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Porcine Pancreatic Tumors Express Known Genes and Pathways L...mentioning

confidence: 97%

See 1 more Smart Citation

Induction of pancreatic neoplasia in theKRAS/TP53Oncopig

Patel

Bailey

Lazenby

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In vascular smooth muscle cells, induction of ornithine decarboxylase by the PI3K and ERK pathways is responsible for IL-4- and IL-13-stimulated cell proliferation [ 41 ]. IL-4 and IL-13 contribute to cancer progression in various cancer types, and several mechanisms have been documented [ 42 , 43 , 44 ]. In response to these cytokines, enhanced glycolysis and glutamine metabolism support growth of pancreatic and breast cancer cells, respectively [ 35 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1

Wang

et al. 2021

IJMS

View full text Add to dashboard Cite

T helper (Th)2 cytokines such as interleukin (IL)-4 and IL-13 control immune function by acting on leukocytes. They also regulate multiple responses in non-hematopoietic cells. During pregnancy, IL-4 and IL-13 facilitate alveologenesis of mammary glands. This particular morphogenesis generates alveoli from existing ducts and requires substantial cell proliferation. Using 3D cultures of primary mouse mammary epithelial cells, we demonstrate that IL-4 and IL-13 promote cell proliferation, leading to enlargement of mammary acini with partially filled lumens. The mitogenic effects of IL-4 and IL-13 are mediated by STAT6 as inhibition of STAT6 suppresses cell proliferation and improves lumen formation. In addition, IL-4 and IL-13 stimulate tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Prolonged treatment with these cytokines leads to increased IRS-1 abundance, which, in turn, amplifies IL-4- and IL-13-stimulated IRS-1 tyrosine phosphorylation. Through signaling crosstalk between IL-4/IL-13 and insulin, a hormone routinely included in mammary cultures, IRS-1 tyrosine phosphorylation is further enhanced. Lowering IRS-1 expression reduces cell proliferation, suggesting that IRS-1 is involved in IL-4- and IL-13-stimulated cell proliferation. Thus, a Th2-dominant cytokine milieu during pregnancy confers mammary gland development by promoting cell proliferation.

show abstract

“…IL-4 and IL-13 act on pancreatic cancer cells mainly through their receptor heterodimers IL-4-receptor-alpha (IL-4Rα) and IL-13Rα1, termed type II IL-4R, via signal pathways of STAT3/6, IRS-ERK/PI3K-Akt and mTOR [ 23 ]. IL-4 can also bind to the type I receptor complex, comprising of IL-4Rα and the common gamma chain (γc) (IL-4/IL-4Rα/γc) [ 13 ], predominantly expressed on hematopoietic cells.…”

Section: Introductionmentioning

confidence: 99%

Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer

Shi

Shen

Kang

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

In search of new therapies for pancreatic cancer, cytokine pathways have attracted increasing interest in recent years. Cytokines play a vital role in the crosstalk between tumour cells and the tumour microenvironment. The related inflammatory cytokines IL-4 and IL-13 can regularly be detected at increased levels in the microenvironment of pancreatic cancer. They share a receptor heterodimer consisting of IL-4Rα and IL-13Rα1. While IL-4Rα induces a more oncogenic phenotype, the role of IL-13Rα1 was yet to be determined. ShRNA-based knockdown of IL-13Rα1 was performed in Capan-1 and MIA PaCa-2. We assessed cell growth and migratory capacities under the influence of IL-13Rα1. Pathway alterations were detected by immunoblot analysis. We now have demonstrated that the loss of IL-13Rα1 induces apoptosis in pancreatic cancer cells. This was associated with an epithelial-to-mesenchymal transition. Loss of IL-13Rα1 also abolished the effects of exogenous IL-4 and IL-13 stimulation. Interestingly, in wild type cells, cytokine stimulation caused a similar increase in migratory capacities as after IL-13Rα1 knockdown. Overall, our results indicate the vital role of IL-13Rα1 in the progression of pancreatic cancer. The differential expression of IL-4Rα and IL-13Rα1 has to be taken into account when considering a cytokine-targeted therapy in pancreatic cancer.

show abstract

Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer

Cited by 51 publications

References 139 publications

Induction of pancreatic neoplasia in theKRAS/TP53Oncopig

Induction of pancreatic neoplasia in theKRAS/TP53Oncopig

IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1

Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer

Contact Info

Product

Resources

About