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CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion
SIMPLE SUMMARY: Ovarian cancer is the most lethal of gynecological malignancies. Although metastasis leads to a bleak prognosis and high mortality, the molecular and cellular processes of ovarian cancer metastasis remain largely unclear. Non-malignant cells including macrophages constitute a unique...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198020/ https://www.ncbi.nlm.nih.gov/pubmed/34206004 http://dx.doi.org/10.3390/cancers13112745 |
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author | Jeong, Miran Wang, Yi-Yue Choi, Ju-Yeon Lim, Myong Cheol Choi, Jung-Hye |
author_facet | Jeong, Miran Wang, Yi-Yue Choi, Ju-Yeon Lim, Myong Cheol Choi, Jung-Hye |
author_sort | Jeong, Miran |
collection | PubMed |
description | SIMPLE SUMMARY: Ovarian cancer is the most lethal of gynecological malignancies. Although metastasis leads to a bleak prognosis and high mortality, the molecular and cellular processes of ovarian cancer metastasis remain largely unclear. Non-malignant cells including macrophages constitute a unique microenvironment that can completely change the nature of malignant cells at various levels. In this study, we found that the expression of chemokine (C-C motif) ligand 7 (CCL7), a soluble inflammatory factor, was enhanced in macrophages stimulated by human ovarian cancer cells as well as peritoneal macrophages from patients with ovarian cancer; CCL7 promoted the invasion of ovarian cancer cells. Our study elucidates the crosstalk between macrophages and ovarian cancer cells that contributes to ovarian cancer metastasis. ABSTRACT: In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis. |
format | Online Article Text |
id | pubmed-8198020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81980202021-06-14 CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion Jeong, Miran Wang, Yi-Yue Choi, Ju-Yeon Lim, Myong Cheol Choi, Jung-Hye Cancers (Basel) Article SIMPLE SUMMARY: Ovarian cancer is the most lethal of gynecological malignancies. Although metastasis leads to a bleak prognosis and high mortality, the molecular and cellular processes of ovarian cancer metastasis remain largely unclear. Non-malignant cells including macrophages constitute a unique microenvironment that can completely change the nature of malignant cells at various levels. In this study, we found that the expression of chemokine (C-C motif) ligand 7 (CCL7), a soluble inflammatory factor, was enhanced in macrophages stimulated by human ovarian cancer cells as well as peritoneal macrophages from patients with ovarian cancer; CCL7 promoted the invasion of ovarian cancer cells. Our study elucidates the crosstalk between macrophages and ovarian cancer cells that contributes to ovarian cancer metastasis. ABSTRACT: In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis. MDPI 2021-06-01 /pmc/articles/PMC8198020/ /pubmed/34206004 http://dx.doi.org/10.3390/cancers13112745 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jeong, Miran Wang, Yi-Yue Choi, Ju-Yeon Lim, Myong Cheol Choi, Jung-Hye CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion |
title | CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion |
title_full | CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion |
title_fullStr | CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion |
title_full_unstemmed | CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion |
title_short | CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion |
title_sort | cc chemokine ligand 7 derived from cancer-stimulated macrophages promotes ovarian cancer cell invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198020/ https://www.ncbi.nlm.nih.gov/pubmed/34206004 http://dx.doi.org/10.3390/cancers13112745 |
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