Chronic inflammation and angiogenesis are associated with colonic carcinogenesis. Enteric glia-derived S100B protein has been proposed as an "ideal bridge", linking colonic inflammation and cancer, given its dual ability to up-regulate nuclear factor-kappaB (NF-κB) transcription via receptor for advanced glycation end products (RAGE) signaling and to sequestrate wild type pro-apoptotic wild type (wt)p53. However, its pro-angiogenic effects on cancer cells are still uninvestigated. To this aim, we evaluated the effect of exogenous S100B (0.05-5 µM) protein alone or in the presence of S100B blocking monoclonal antibody (mAb) (1:105-1:104 v/v diluted) on (1) cultured Caco-2 cells proliferation, migration and invasiveness in vitro, respectively by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-formazan, wound healing and matrigel invasion assays and (2) its effect on the release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) by ELISA and immunofluorescence analyses. The effect of S100B alone or in the presence of S100BmAb was then investigated on RAGE/pAkt/mammalian target of rapamycin (mTOR) signaling pathway by immunoblot analysis. Our results showed that S100B markedly increases proliferation and invasiveness of Caco-2 cells, through the release of pro-angiogenic VEGF and NO paralleled to a significant decrease of wtp53 expression mediated by RAGE-p38 mitogen-activated protein kinase (MAPK)/pAkt-mTOR and hypoxia-inducible factor 1-alpha (HIF1α) pathways. Such effects were counteracted by S100BmAb, indicating that S100B targeting is a potential approach to inhibit colon carcinoma proliferation and angiogenesis.

S100B protein stimulates proliferation and angiogenic mediators release through RAGE/pAkt/mTOR pathway in human colon adenocarcinoma Caco-2 Cells / Seguella, Luisa; Capuano, Riccardo; Pesce, Mirella; Annunziata, Giuseppe; Pesce, Marcella; de Conno, Barbara; Sarnelli, Giovanni; Aurino, Laura; Esposito, Giuseppe. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 20:13(2019). [10.3390/ijms20133240]

S100B protein stimulates proliferation and angiogenic mediators release through RAGE/pAkt/mTOR pathway in human colon adenocarcinoma Caco-2 Cells

Luisa Seguella;Riccardo Capuano;Mirella Pesce;Giuseppe Esposito
2019

Abstract

Chronic inflammation and angiogenesis are associated with colonic carcinogenesis. Enteric glia-derived S100B protein has been proposed as an "ideal bridge", linking colonic inflammation and cancer, given its dual ability to up-regulate nuclear factor-kappaB (NF-κB) transcription via receptor for advanced glycation end products (RAGE) signaling and to sequestrate wild type pro-apoptotic wild type (wt)p53. However, its pro-angiogenic effects on cancer cells are still uninvestigated. To this aim, we evaluated the effect of exogenous S100B (0.05-5 µM) protein alone or in the presence of S100B blocking monoclonal antibody (mAb) (1:105-1:104 v/v diluted) on (1) cultured Caco-2 cells proliferation, migration and invasiveness in vitro, respectively by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-formazan, wound healing and matrigel invasion assays and (2) its effect on the release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) by ELISA and immunofluorescence analyses. The effect of S100B alone or in the presence of S100BmAb was then investigated on RAGE/pAkt/mammalian target of rapamycin (mTOR) signaling pathway by immunoblot analysis. Our results showed that S100B markedly increases proliferation and invasiveness of Caco-2 cells, through the release of pro-angiogenic VEGF and NO paralleled to a significant decrease of wtp53 expression mediated by RAGE-p38 mitogen-activated protein kinase (MAPK)/pAkt-mTOR and hypoxia-inducible factor 1-alpha (HIF1α) pathways. Such effects were counteracted by S100BmAb, indicating that S100B targeting is a potential approach to inhibit colon carcinoma proliferation and angiogenesis.
2019
Akt/mTOR; Caco-2 cell proliferation; RAGE; S100B; VEGF; angiogenic mediators; colorectal carcinoma; tumor microenvironment.
01 Pubblicazione su rivista::01a Articolo in rivista
S100B protein stimulates proliferation and angiogenic mediators release through RAGE/pAkt/mTOR pathway in human colon adenocarcinoma Caco-2 Cells / Seguella, Luisa; Capuano, Riccardo; Pesce, Mirella; Annunziata, Giuseppe; Pesce, Marcella; de Conno, Barbara; Sarnelli, Giovanni; Aurino, Laura; Esposito, Giuseppe. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 20:13(2019). [10.3390/ijms20133240]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1415146
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