Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-α

Oxytocin (OXT) and its receptor (OXTR) are present in the gastrointestinal system and are involved in gastrointestinal tumorigenesis. However, the effect of OXTR signaling on the development of colorectal cancer (CRC) and its underlying mechanisms remain unexplored. To address these issues, we first...

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Main Authors: Mingxing Ma, Li Li, He Chen, Yong Feng
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-12-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnins.2019.01317/full
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author Mingxing Ma
Li Li
He Chen
Yong Feng
author_facet Mingxing Ma
Li Li
He Chen
Yong Feng
author_sort Mingxing Ma
collection DOAJ
description Oxytocin (OXT) and its receptor (OXTR) are present in the gastrointestinal system and are involved in gastrointestinal tumorigenesis. However, the effect of OXTR signaling on the development of colorectal cancer (CRC) and its underlying mechanisms remain unexplored. To address these issues, we first examined the expressions of OXT, OXTR, and several cancer-associated proteins using colon “tissue chips” from a spectrum of malignant progression of the colon, which included normal colon tissue, chronic colitis, colorectal adenoma, and colorectal adenocarcinoma (CAC). The results showed that the expressions of OXT and OXTR decreased gradually with the malignant progression of the disease. Stimulation of CAC tissues with OXT increased OXTR expression while down-regulated FAPα and CCL-2 protein expressions in a concentration- and time-dependent manner. Moreover, cell invasion experiment showed that OXT treatment reduced the invasion ability of colon cancer cells and blocking OXTR with atosiban blocked OXT-reduced invasion ability of human colon cancer cell lines Ls174T and SW480. The results indicate that OXT has the potential to inhibit CRC development via down-regulating the immunosuppressive proteins FAPα and CCL-2. When the OXTR signaling is weakened, colon tissues may transform to CRC. These findings also highlight the possibility of applying OXT to inhibit CRC development directly.
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spelling doaj.art-3e158c4b741f424aad28650c917af4042022-12-22T01:19:48ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-12-011310.3389/fnins.2019.01317458589Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-αMingxing Ma0Li Li1He Chen2Yong Feng3Department of Colorectal Surgery, Shengjing Hospital, China Medical University, Shenyang, ChinaDepartment of Forensic Medicine, Harbin Medical University, Harbin, ChinaDepartment of Forensic Medicine, Harbin Medical University, Harbin, ChinaDepartment of General Surgery, Affiliated Shengjing Hospital, China Medical University, Shenyang, ChinaOxytocin (OXT) and its receptor (OXTR) are present in the gastrointestinal system and are involved in gastrointestinal tumorigenesis. However, the effect of OXTR signaling on the development of colorectal cancer (CRC) and its underlying mechanisms remain unexplored. To address these issues, we first examined the expressions of OXT, OXTR, and several cancer-associated proteins using colon “tissue chips” from a spectrum of malignant progression of the colon, which included normal colon tissue, chronic colitis, colorectal adenoma, and colorectal adenocarcinoma (CAC). The results showed that the expressions of OXT and OXTR decreased gradually with the malignant progression of the disease. Stimulation of CAC tissues with OXT increased OXTR expression while down-regulated FAPα and CCL-2 protein expressions in a concentration- and time-dependent manner. Moreover, cell invasion experiment showed that OXT treatment reduced the invasion ability of colon cancer cells and blocking OXTR with atosiban blocked OXT-reduced invasion ability of human colon cancer cell lines Ls174T and SW480. The results indicate that OXT has the potential to inhibit CRC development via down-regulating the immunosuppressive proteins FAPα and CCL-2. When the OXTR signaling is weakened, colon tissues may transform to CRC. These findings also highlight the possibility of applying OXT to inhibit CRC development directly.https://www.frontiersin.org/article/10.3389/fnins.2019.01317/fullcolorectal cancerfibroblast activation protein-αoxytocinoxytocin receptormetastasis
spellingShingle Mingxing Ma
Li Li
He Chen
Yong Feng
Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-α
Frontiers in Neuroscience
colorectal cancer
fibroblast activation protein-α
oxytocin
oxytocin receptor
metastasis
title Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-α
title_full Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-α
title_fullStr Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-α
title_full_unstemmed Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-α
title_short Oxytocin Inhibition of Metastatic Colorectal Cancer by Suppressing the Expression of Fibroblast Activation Protein-α
title_sort oxytocin inhibition of metastatic colorectal cancer by suppressing the expression of fibroblast activation protein α
topic colorectal cancer
fibroblast activation protein-α
oxytocin
oxytocin receptor
metastasis
url https://www.frontiersin.org/article/10.3389/fnins.2019.01317/full
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AT hechen oxytocininhibitionofmetastaticcolorectalcancerbysuppressingtheexpressionoffibroblastactivationproteina
AT yongfeng oxytocininhibitionofmetastaticcolorectalcancerbysuppressingtheexpressionoffibroblastactivationproteina