Glucagon-like petide-2 acts on colon cancer myofibroblasts to stimulate proliferation, migration and invasion of both myofibroblasts and cancer cells via the IGF pathway

Shawe-Taylor, Marianne; Kumar, J. Dinesh; Holden, Whitney; Dodd, Steven W.; Varga, Ákos János; Giger, Olivier; Varró, Andrea; Dockray, Graham J.

doi:10.1016/j.peptides.2017.03.008

Cited by 16 publications

(19 citation statements)

References 39 publications

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“…Growth of neural progenitor cells was assessed by determining the number and the size of the induced neurospheres and using CCK8 assay. The P4 BMSCs were seeded into a 24‐well plate (10 5 cells/cm 2 ) in quadruplicate and cultured in DMEM medium for 4 hours; the medium was subsequently replaced by NeuroCult medium supplemented with the following combinations: EGF (20 μg/mL, Lot: OQK0412021, R&D, Minneapolis, MN, USA) and bFGF (20 μg/mL, Lot: HKW11714121, R&D), IGFBP‐4 (0.5 μg/mL), EGF + bFGF + IGFBP‐4, AG1024 (20 μM), AG1024 + EGF + bFGF + IGFBP‐4, FH535 (20 μM), and FH535 + EGF + bFGF + IGFBP‐4. Half the volume of the medium was replaced every 2 days, and cells were photographed using CellSens Standard imaging software under a fluorescent inverted microscope (Olympus IX71) equipped with an Olympus camera (DP73).…”

Section: Methodsmentioning

confidence: 99%

Insulin‐like growth factor binding protein 4 inhibits proliferation of bone marrow mesenchymal stem cells and enhances growth of neurospheres derived from the stem cells

Hao

et al. 2018

Cell Biochemistry & Function

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Insulin-like growth factor binding protein 4 (IGFBP-4) was reported to trigger cellular senescence and reduce cell growth of bone marrow mesenchymal stem cells (BMSCs), but its contribution to neurogenic differentiation of BMSCs remains unknown. In the present study, BMSCs were isolated from the femur and tibia of young rats to investigate effects of IGFBP-4 on BMSC proliferation and growth of neurospheres derived from BMSCs. Bone marrow mesenchymal stem cell proliferation was assessed using CCK-8 after treatment with IGFBP-4 or blockers of IGF-IR and β-catenin. Phosphorylation levels of Akt, Erk, and p38 in BMSCs were analysed by Western blotting. Bone marrow mesenchymal stem cells were induced into neural lineages in NeuroCult medium; the number and the size of BMSC-derived neurospheres were counted after treatment with IGFBP-4 or the blockers. It was shown that addition of IGFBP-4 inhibited BMSC proliferation and immunodepletion of IGFBP-4 increased the proliferation. The blockade of IGF-IR with AG1024 increased BMSC proliferation and reversed IGFBP-4-induced proliferation inhibition; however, blocking of β-catenin with FH535 did not. p-Erk was significantly decreased in IGFBP-4-treated BMSCs. IGFBP-4 promoted the growth of neurospheres derived from BMSCs, as manifested by the increases in the number and the size of the derived neurospheres. Both AG1024 and FH535 inhibited the formation of NeuroCult-induced neurospheres, but FH535 significantly inhibited the growth of neurospheres in NeuroCult medium with EGF, bFGF, and IGFBP-4. The data suggested that IGFBP-4 inhibits BMSC proliferation through IGF-IR pathway and promotes growth of BMSC-derived neurospheres via stabilizing β-catenin.

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Section: Methodsmentioning

confidence: 99%

Insulin‐like growth factor binding protein 4 inhibits proliferation of bone marrow mesenchymal stem cells and enhances growth of neurospheres derived from the stem cells

Hao

et al. 2018

Cell Biochemistry & Function

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“…A clinical investigation also indicated that fasting serum insulin is an independent risk factor for benign proliferative breast disease which is associated with early stages of breast cancer development [29]. Insulin induces downregulation of Ecadherin expression, accompanied with an increase in N-cadherin and vimentin expression in mammary non-tumorigenic epithelial cell line MCF10A [30] suggesting that insulin has a potential to Insulin and insulin-like growth factor promotes EMT in gastric, colon, hepatic and breast cancer [36][37][38][39][40]. Hyperinsulinemia is a key risk factor for patients with breast cancer.…”

Section: Discussionmentioning

confidence: 99%

NR2F2 Plays a Major Role in Insulin-induced Epithelial-Mesenchymal Transition in Breast Cancer Cells

Xia

Hou

Kang

et al. 2019

Preprint

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The failure of treatment for breast cancer usually results from distant metastasis in which the epithelial-mesenchymal transition (EMT) plays a critical role. Hyperinsulinemia, the hallmark of Type 2 diabetes mellitus (T2DM), has been regarded as a key risk factor for the progression of breast cancer. Nuclear receptor subfamily 2, group F member 2 (NR2F2) has been implicated in the development of breast cancer, however its contribution to insulin- induced EMT in breast cancer remains unclear. Overexpression and knockdown of NR2F2 was used in two breast cancer cell lines, MCF-7 and MDA-MB-231 to investigate potential mechanisms by which NR2F2 leads to insulin-mediated EMT. Insulin stimulation of these cells increased NR2F2 expression levels and promoted invasion and cell migration accompanied by alterations in EMT-related molecular markers. Overexpression of NR2F2 and NR2F2 knockdown demonstrated that NR2F2 expression was positively correlated with cell invasion, migration and the expression of N-cadherin and vimentin. In contrast,, NR2F2 had an inverse correlation with E-cadherin expression. In MDA-MB-231, both insulin-induced cell invasion and migration and EMT-related marker alteration were abolished by NR2F2 knockdown. These results suggest that NR2F2 plays a critical role in insulin-mediated breast cancer cell invasion, migration through its effect on EMT.

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“…These results indicated that jejunum epithelial cell proliferation will be inhibited after blocking IGF‐1 signalling pathway, which is consistent with the previous studies. Shawe‐Taylor et al, () showed that the addition of GLP‐2 significantly promote the proliferation, migration and differentiation of caecal fibroblasts; however, the biological effects of GLP‐2 disappeared after addition of IGF‐1R inhibitor. These results indicate that GLP‐2 indirectly promotes cell proliferation mainly through IGF‐1 pathway.…”

Section: Discussionmentioning

confidence: 99%

Aspartame supplementation in starter accelerates small intestinal epithelial cell cycle and stimulates secretion of glucagon‐like peptide‐2 in pre‐weaned lambs

Sun

Liu

Mao

et al. 2019

Animal Physiology Nutrition

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The objective of this study was to test the hypothesis that aspartame supplementation in starter diet accelerates small intestinal cell cycle by stimulating secretion and expression of glucagon‐like peptide −2 (GLP‐2) in pre‐weaned lambs using animal and cell culture experiments. In vivo, twelve 14‐day‐old lambs were selected and allocated randomly to two groups; one was treated with plain starter diet (Con, n = 6) and the other was treated with starter supplemented with 200 mg of aspartame/kg starter (APM, n = 6). Results showed that the lambs received APM treatment for 35 d had higher (p < .05) GLP‐2 concentration in the plasma and greater jejunum weight/live body weight (BW) and jejunal crypt depth. Furthermore, APM treatment significantly upregulated (p < .05) the mRNA expression of cyclin D1 in duodenum; and cyclin A2, cyclin D1, cyclin‐dependent kinases 6 (CDK6) in jejunum; and cyclin A2, cyclin D1, CDK4 in ileum. Moreover, APM treatment increased (p < .05) the mRNA expression of glucagon (GCG), insulin‐like growth factor 1 (IGF‐1) in the jejunum and ileum and mRNA expression of GLP‐2 receptor (GLP‐2R) in the jejunum. In vitro, when jejunal cells were treated with GLP‐2 for 2 hr, the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) OD, IGF‐1 concentration, and the mRNA expression of IGF‐1, cyclin D1 and CDK6 were increased (p < .05). Furthermore, IGF‐1 receptor (IGF‐1R) inhibitor decreased (p < .05) the mRNA expression of IGF‐1, cyclin A2, cyclin D1 and CDK6 in GLP‐2 treatment jejunal cells. These results suggest that aspartame supplementation in starter accelerates small intestinal cell cycle that may, in part, be related to stimulate secretion and expression of GLP‐2 in pre‐weaning lambs. Furthermore, GLP‐2 can indirectly promote the proliferation of jejunal cells mainly through the IGF‐1 pathway. These findings provide new insights into nutritional interventions that promote the development of small intestines in young ruminants.

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Glucagon-like petide-2 acts on colon cancer myofibroblasts to stimulate proliferation, migration and invasion of both myofibroblasts and cancer cells via the IGF pathway

Cited by 16 publications

References 39 publications

Insulin‐like growth factor binding protein 4 inhibits proliferation of bone marrow mesenchymal stem cells and enhances growth of neurospheres derived from the stem cells

Insulin‐like growth factor binding protein 4 inhibits proliferation of bone marrow mesenchymal stem cells and enhances growth of neurospheres derived from the stem cells

NR2F2 Plays a Major Role in Insulin-induced Epithelial-Mesenchymal Transition in Breast Cancer Cells

Aspartame supplementation in starter accelerates small intestinal epithelial cell cycle and stimulates secretion of glucagon‐like peptide‐2 in pre‐weaned lambs

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