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Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism

The antimicrobial peptide cathelicidin inhibits development of colitis-associated colon cancer. However, the role of cathelicidin in colon cancer metastasis remains unknown. We hypothesized that cathelicidin is effective in inhibiting colon cancer metastasis. Human colon cancer HT-29 cells were inje...

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Autores principales: Wang, Jiani, Cheng, Michelle, Law, Ivy K.M., Ortiz, Christina, Sun, Mingjun, Koon, Hon Wai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389776/
https://www.ncbi.nlm.nih.gov/pubmed/30847383
http://dx.doi.org/10.1016/j.omto.2019.01.004
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author Wang, Jiani
Cheng, Michelle
Law, Ivy K.M.
Ortiz, Christina
Sun, Mingjun
Koon, Hon Wai
author_facet Wang, Jiani
Cheng, Michelle
Law, Ivy K.M.
Ortiz, Christina
Sun, Mingjun
Koon, Hon Wai
author_sort Wang, Jiani
collection PubMed
description The antimicrobial peptide cathelicidin inhibits development of colitis-associated colon cancer. However, the role of cathelicidin in colon cancer metastasis remains unknown. We hypothesized that cathelicidin is effective in inhibiting colon cancer metastasis. Human colon cancer HT-29 cells were injected intravenously into nude mice. Control HA-tagged adeno-associated virus (HA-AAV) or cathelicidin-overexpressing AAV (CAMP-HA-AAV) were injected intravenously into nude mice on the same day. Four weeks later, the nude mice were assessed for lung and liver metastases. Human colon cancer SW620 cells were used to study the effect of cathelicidin on cell migration and cytoskeleton. Incubation of SW620 cells with cathelicidin dose-dependently reduced cell migration, disrupted cytoskeletal structure, and reduced βIII-tubulin (TUBB3) mRNA expression. The addition of the P2RX7 antagonist KN62, but not the FPRL1 antagonist WRW4, prevented the LL-37-mediated inhibition of cell migration and TUBB3 mRNA expression. The CAMP-HA-AAV-overexpressing group showed significantly reduced human CK20 protein (by 60%) and TUBB3 mRNA expression (by 40%) in the lungs and liver of the HT-29-loaded nude mice, compared to the HA-AAV control group. Intraperitoneal injection of KN62 reversed the CAMP-HA-AAV-mediated inhibition of human CK20 and TUBB3 expression in the lungs and liver of HT-29-loaded nude mice. In conclusion, cathelicidin inhibits colon cancer metastasis via a P2RX7-dependent pathway.
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spelling pubmed-63897762019-03-07 Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism Wang, Jiani Cheng, Michelle Law, Ivy K.M. Ortiz, Christina Sun, Mingjun Koon, Hon Wai Mol Ther Oncolytics Article The antimicrobial peptide cathelicidin inhibits development of colitis-associated colon cancer. However, the role of cathelicidin in colon cancer metastasis remains unknown. We hypothesized that cathelicidin is effective in inhibiting colon cancer metastasis. Human colon cancer HT-29 cells were injected intravenously into nude mice. Control HA-tagged adeno-associated virus (HA-AAV) or cathelicidin-overexpressing AAV (CAMP-HA-AAV) were injected intravenously into nude mice on the same day. Four weeks later, the nude mice were assessed for lung and liver metastases. Human colon cancer SW620 cells were used to study the effect of cathelicidin on cell migration and cytoskeleton. Incubation of SW620 cells with cathelicidin dose-dependently reduced cell migration, disrupted cytoskeletal structure, and reduced βIII-tubulin (TUBB3) mRNA expression. The addition of the P2RX7 antagonist KN62, but not the FPRL1 antagonist WRW4, prevented the LL-37-mediated inhibition of cell migration and TUBB3 mRNA expression. The CAMP-HA-AAV-overexpressing group showed significantly reduced human CK20 protein (by 60%) and TUBB3 mRNA expression (by 40%) in the lungs and liver of the HT-29-loaded nude mice, compared to the HA-AAV control group. Intraperitoneal injection of KN62 reversed the CAMP-HA-AAV-mediated inhibition of human CK20 and TUBB3 expression in the lungs and liver of HT-29-loaded nude mice. In conclusion, cathelicidin inhibits colon cancer metastasis via a P2RX7-dependent pathway. American Society of Gene & Cell Therapy 2019-01-29 /pmc/articles/PMC6389776/ /pubmed/30847383 http://dx.doi.org/10.1016/j.omto.2019.01.004 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Wang, Jiani
Cheng, Michelle
Law, Ivy K.M.
Ortiz, Christina
Sun, Mingjun
Koon, Hon Wai
Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism
title Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism
title_full Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism
title_fullStr Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism
title_full_unstemmed Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism
title_short Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism
title_sort cathelicidin suppresses colon cancer metastasis via a p2rx7-dependent mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389776/
https://www.ncbi.nlm.nih.gov/pubmed/30847383
http://dx.doi.org/10.1016/j.omto.2019.01.004
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