Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo.
Cancer associated fibroblasts (CAFs) are responsible for tumor growth, angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP)-9 secreted from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) h...
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2014
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oai:doaj.org-article:380d84cde8e340c4b51e82397041f59f2021-11-18T08:30:44ZMatrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo.1932-620310.1371/journal.pone.0089605https://doaj.org/article/380d84cde8e340c4b51e82397041f59f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586907/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Cancer associated fibroblasts (CAFs) are responsible for tumor growth, angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP)-9 secreted from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) have been reported to have anti-tumor effects on diverse types of malignancies. Fat-1 mice, which can convert omega-6 to omega-3 PUFA independent of diet, are useful to investigate the functions of endogenous omega-3 PUFA. To examine the effect of omega-3 PUFA on tumorigenesis, TC-1 cells, a murine epithelial cell line immortalized by human papillomavirus (HPV) oncogenes, were injected subcutaneously into fat-1 or wild type mice. Tumor growth and angiogenesis of the TC-1 tumor were significantly suppressed in fat-1 compared to wild type mice. cDNA microarray of the tumors derived from fat-1 and wild type mice revealed that MMP-9 is downregulated in fat-1 mice. Immunohistochemical study demonstrated immunoreactivity for MMP-9 in the tumor stromal fibroblasts was diffusely positive in wild type whereas focal in fat-1 mice. MMP-9 was expressed in primary cultured fibroblasts isolated from fat-1 and wild type mice but was not expressed in TC-1 cells. Co-culture of fibroblasts with TC-1 cells enhanced the expression and the proteinase activity of MMP-9, although the protease activity of MMP-9 in fat-1-derived fibroblasts was lower than that in wild type fibroblasts. Our data suggests that omega-3 PUFAs suppress MMP-9 induction and tumor angiogenesis. These findings may provide insight into mechanisms by which omega-3 PUFAs exert anti-tumor effects by modulating tumor microenvironment.Ayumi TaguchiKei KawanaKensuke TomioAki YamashitaYosuke IsobeKazunori NagasakaKaori KogaTomoko InoueHaruka NishidaSatoko KojimaKatsuyuki AdachiYoko MatsumotoTakahide ArimotoOsamu Wada-HiraikeKatsutoshi OdaJing X KangHiroyuki AraiMakoto AritaYutaka OsugaTomoyuki FujiiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89605 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Ayumi Taguchi Kei Kawana Kensuke Tomio Aki Yamashita Yosuke Isobe Kazunori Nagasaka Kaori Koga Tomoko Inoue Haruka Nishida Satoko Kojima Katsuyuki Adachi Yoko Matsumoto Takahide Arimoto Osamu Wada-Hiraike Katsutoshi Oda Jing X Kang Hiroyuki Arai Makoto Arita Yutaka Osuga Tomoyuki Fujii Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. |
| description |
Cancer associated fibroblasts (CAFs) are responsible for tumor growth, angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP)-9 secreted from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) have been reported to have anti-tumor effects on diverse types of malignancies. Fat-1 mice, which can convert omega-6 to omega-3 PUFA independent of diet, are useful to investigate the functions of endogenous omega-3 PUFA. To examine the effect of omega-3 PUFA on tumorigenesis, TC-1 cells, a murine epithelial cell line immortalized by human papillomavirus (HPV) oncogenes, were injected subcutaneously into fat-1 or wild type mice. Tumor growth and angiogenesis of the TC-1 tumor were significantly suppressed in fat-1 compared to wild type mice. cDNA microarray of the tumors derived from fat-1 and wild type mice revealed that MMP-9 is downregulated in fat-1 mice. Immunohistochemical study demonstrated immunoreactivity for MMP-9 in the tumor stromal fibroblasts was diffusely positive in wild type whereas focal in fat-1 mice. MMP-9 was expressed in primary cultured fibroblasts isolated from fat-1 and wild type mice but was not expressed in TC-1 cells. Co-culture of fibroblasts with TC-1 cells enhanced the expression and the proteinase activity of MMP-9, although the protease activity of MMP-9 in fat-1-derived fibroblasts was lower than that in wild type fibroblasts. Our data suggests that omega-3 PUFAs suppress MMP-9 induction and tumor angiogenesis. These findings may provide insight into mechanisms by which omega-3 PUFAs exert anti-tumor effects by modulating tumor microenvironment. |
| format |
article |
| author |
Ayumi Taguchi Kei Kawana Kensuke Tomio Aki Yamashita Yosuke Isobe Kazunori Nagasaka Kaori Koga Tomoko Inoue Haruka Nishida Satoko Kojima Katsuyuki Adachi Yoko Matsumoto Takahide Arimoto Osamu Wada-Hiraike Katsutoshi Oda Jing X Kang Hiroyuki Arai Makoto Arita Yutaka Osuga Tomoyuki Fujii |
| author_facet |
Ayumi Taguchi Kei Kawana Kensuke Tomio Aki Yamashita Yosuke Isobe Kazunori Nagasaka Kaori Koga Tomoko Inoue Haruka Nishida Satoko Kojima Katsuyuki Adachi Yoko Matsumoto Takahide Arimoto Osamu Wada-Hiraike Katsutoshi Oda Jing X Kang Hiroyuki Arai Makoto Arita Yutaka Osuga Tomoyuki Fujii |
| author_sort |
Ayumi Taguchi |
| title |
Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. |
| title_short |
Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. |
| title_full |
Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. |
| title_fullStr |
Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. |
| title_full_unstemmed |
Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. |
| title_sort |
matrix metalloproteinase (mmp)-9 in cancer-associated fibroblasts (cafs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/380d84cde8e340c4b51e82397041f59f |
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