Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines
Interactions between pancreatic cancer cells and pancreatic stellate cells (PSCs) play an important role in the progression of pancreatic cancer. Recent studies have shown that cellular senescence and senescence-associated secretory phenotype factors play roles in the progression of cancer. This stu...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/9275 |
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| author | Tetsuya Takikawa Shin Hamada Ryotaro Matsumoto Yu Tanaka Fumiya Kataoka Akira Sasaki Atsushi Masamune |
| author_facet | Tetsuya Takikawa Shin Hamada Ryotaro Matsumoto Yu Tanaka Fumiya Kataoka Akira Sasaki Atsushi Masamune |
| author_sort | Tetsuya Takikawa |
| collection | DOAJ |
| description | Interactions between pancreatic cancer cells and pancreatic stellate cells (PSCs) play an important role in the progression of pancreatic cancer. Recent studies have shown that cellular senescence and senescence-associated secretory phenotype factors play roles in the progression of cancer. This study aimed to clarify the effects of senescence-induced PSCs on pancreatic cancer cells. Senescence was induced in primary-cultured human PSCs (hPSCs) through treatment with hydrogen peroxide or gemcitabine. Microarray and Gene Ontology analyses showed the alterations in genes and pathways related to cellular senescence and senescence-associated secretory phenotype factors, including the upregulation of C-X-C motif chemokine ligand (CXCL)-1, CXCL2, and CXCL3 through the induction of senescence in hPSCs. Conditioned media of senescent hPSCs increased the proliferation—as found in an assessment with a BrdU incorporation assay—and migration—as found in an assessment with wound-healing and two-chamber assays—of pancreatic cancer AsPC-1 and MIAPaca-2 cell lines. SB225002, a selective CXCR2 antagonist, and SCH-527123, a CXCR1/CXCR2 antagonist, attenuated the effects of conditioned media of senescent hPSCs on the proliferation and migration of pancreatic cancer cells. These results suggest a role of CXCLs as senescence-associated secretory phenotype factors in the interaction between senescent hPSCs and pancreatic cancer cells. Senescent PSCs might be novel therapeutic targets for pancreatic cancer. |
| first_indexed | 2024-03-09T09:54:59Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T09:54:59Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-076d765084cd43d9b9ac573bdab9a7e22023-12-01T23:48:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316927510.3390/ijms23169275Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell LinesTetsuya Takikawa0Shin Hamada1Ryotaro Matsumoto2Yu Tanaka3Fumiya Kataoka4Akira Sasaki5Atsushi Masamune6Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanInteractions between pancreatic cancer cells and pancreatic stellate cells (PSCs) play an important role in the progression of pancreatic cancer. Recent studies have shown that cellular senescence and senescence-associated secretory phenotype factors play roles in the progression of cancer. This study aimed to clarify the effects of senescence-induced PSCs on pancreatic cancer cells. Senescence was induced in primary-cultured human PSCs (hPSCs) through treatment with hydrogen peroxide or gemcitabine. Microarray and Gene Ontology analyses showed the alterations in genes and pathways related to cellular senescence and senescence-associated secretory phenotype factors, including the upregulation of C-X-C motif chemokine ligand (CXCL)-1, CXCL2, and CXCL3 through the induction of senescence in hPSCs. Conditioned media of senescent hPSCs increased the proliferation—as found in an assessment with a BrdU incorporation assay—and migration—as found in an assessment with wound-healing and two-chamber assays—of pancreatic cancer AsPC-1 and MIAPaca-2 cell lines. SB225002, a selective CXCR2 antagonist, and SCH-527123, a CXCR1/CXCR2 antagonist, attenuated the effects of conditioned media of senescent hPSCs on the proliferation and migration of pancreatic cancer cells. These results suggest a role of CXCLs as senescence-associated secretory phenotype factors in the interaction between senescent hPSCs and pancreatic cancer cells. Senescent PSCs might be novel therapeutic targets for pancreatic cancer.https://www.mdpi.com/1422-0067/23/16/9275cancer-associated fibroblastcellular senescencechemokinemyofibroblastpancreatic ductal adenocarcinomasenescence-associated secretory phenotype |
| spellingShingle | Tetsuya Takikawa Shin Hamada Ryotaro Matsumoto Yu Tanaka Fumiya Kataoka Akira Sasaki Atsushi Masamune Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines International Journal of Molecular Sciences cancer-associated fibroblast cellular senescence chemokine myofibroblast pancreatic ductal adenocarcinoma senescence-associated secretory phenotype |
| title | Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines |
| title_full | Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines |
| title_fullStr | Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines |
| title_full_unstemmed | Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines |
| title_short | Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines |
| title_sort | senescent human pancreatic stellate cells secrete cxcr2 agonist cxcls to promote proliferation and migration of human pancreatic cancer aspc 1 and miapaca 2 cell lines |
| topic | cancer-associated fibroblast cellular senescence chemokine myofibroblast pancreatic ductal adenocarcinoma senescence-associated secretory phenotype |
| url | https://www.mdpi.com/1422-0067/23/16/9275 |
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