CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion
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 o...
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MDPI AG
2021-06-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/13/11/2745 |
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author | Miran Jeong Yi-Yue Wang Ju-Yeon Choi Myong Cheol Lim Jung-Hye Choi |
author_facet | Miran Jeong Yi-Yue Wang Ju-Yeon Choi Myong Cheol Lim Jung-Hye Choi |
author_sort | Miran Jeong |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-10T10:49:05Z |
format | Article |
id | doaj.art-afb8b9c683804287b877ef8e616763e5 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T10:49:05Z |
publishDate | 2021-06-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-afb8b9c683804287b877ef8e616763e52023-11-21T22:25:31ZengMDPI AGCancers2072-66942021-06-011311274510.3390/cancers13112745CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell InvasionMiran Jeong0Yi-Yue Wang1Ju-Yeon Choi2Myong Cheol Lim3Jung-Hye Choi4Division of Molecular Biology, College of Pharmacy, Kyung Hee University, Seoul 02447, KoreaDepartment of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 02447, KoreaDepartment of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 02447, KoreaDivision of Tumor Immunology, Center for Gynecologic Cancer & Center for Clinical Trials, National Cancer Center, Goyang 10408, KoreaDivision of Molecular Biology, College of Pharmacy, Kyung Hee University, Seoul 02447, KoreaIn 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.https://www.mdpi.com/2072-6694/13/11/2745CCL7CCR3tumor-associated macrophagesovarian cancer |
spellingShingle | Miran Jeong Yi-Yue Wang Ju-Yeon Choi Myong Cheol Lim Jung-Hye Choi CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion Cancers CCL7 CCR3 tumor-associated macrophages ovarian cancer |
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 | CCL7 CCR3 tumor-associated macrophages ovarian cancer |
url | https://www.mdpi.com/2072-6694/13/11/2745 |
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