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CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells

Peritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cel...

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Autores principales: Lepsenyi, Mattias, Algethami, Nader, Al-Haidari, Amr A., Algaber, Anwar, Syk, Ingvar, Rahman, Milladur, Thorlacius, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318971/
https://www.ncbi.nlm.nih.gov/pubmed/34115261
http://dx.doi.org/10.1007/s10585-021-10103-0
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author Lepsenyi, Mattias
Algethami, Nader
Al-Haidari, Amr A.
Algaber, Anwar
Syk, Ingvar
Rahman, Milladur
Thorlacius, Henrik
author_facet Lepsenyi, Mattias
Algethami, Nader
Al-Haidari, Amr A.
Algaber, Anwar
Syk, Ingvar
Rahman, Milladur
Thorlacius, Henrik
author_sort Lepsenyi, Mattias
collection PubMed
description Peritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10585-021-10103-0.
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spelling pubmed-83189712021-08-13 CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells Lepsenyi, Mattias Algethami, Nader Al-Haidari, Amr A. Algaber, Anwar Syk, Ingvar Rahman, Milladur Thorlacius, Henrik Clin Exp Metastasis Research Paper Peritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10585-021-10103-0. Springer Netherlands 2021-06-11 2021 /pmc/articles/PMC8318971/ /pubmed/34115261 http://dx.doi.org/10.1007/s10585-021-10103-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Paper
Lepsenyi, Mattias
Algethami, Nader
Al-Haidari, Amr A.
Algaber, Anwar
Syk, Ingvar
Rahman, Milladur
Thorlacius, Henrik
CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
title CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
title_full CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
title_fullStr CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
title_full_unstemmed CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
title_short CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
title_sort cxcl2-cxcr2 axis mediates αv integrin-dependent peritoneal metastasis of colon cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318971/
https://www.ncbi.nlm.nih.gov/pubmed/34115261
http://dx.doi.org/10.1007/s10585-021-10103-0
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