Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in vari...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-06-01
|
| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-02910-3 |
| _version_ | 1828330704908320768 |
|---|---|
| author | Ying-Cheng Chen Ying-Wei Lan Shiaw-Min Huang Chih-Ching Yen Wei Chen Wan-Ju Wu Theresa Staniczek Kowit-Yu Chong Chuan-Mu Chen |
| author_facet | Ying-Cheng Chen Ying-Wei Lan Shiaw-Min Huang Chih-Ching Yen Wei Chen Wan-Ju Wu Theresa Staniczek Kowit-Yu Chong Chuan-Mu Chen |
| author_sort | Ying-Cheng Chen |
| collection | DOAJ |
| description | Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC. Methods To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft. Results An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice. Conclusions Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT. |
| first_indexed | 2024-04-13T20:43:23Z |
| format | Article |
| id | doaj.art-39e085c311144a6f9bb87bfe4f956564 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T20:43:23Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-39e085c311144a6f9bb87bfe4f9565642022-12-22T02:30:47ZengBMCStem Cell Research & Therapy1757-65122022-06-0113111710.1186/s13287-022-02910-3Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse modelYing-Cheng Chen0Ying-Wei Lan1Shiaw-Min Huang2Chih-Ching Yen3Wei Chen4Wan-Ju Wu5Theresa Staniczek6Kowit-Yu Chong7Chuan-Mu Chen8Department of Life Sciences, and Ph.D. Program in Translational Medicine, College of Life Sciences, National Chung Hsing UniversityDepartment of Life Sciences, and Ph.D. Program in Translational Medicine, College of Life Sciences, National Chung Hsing UniversityBioresource Collection and Research Center, Food Industry Research and Development InstituteDepartment of Internal Medicine, China Medical University Hospital, and College of Health Care, China Medical UniversityDivision of Pulmonary and Critical Care Medicine, Chia-Yi Christian HospitalDepartment of Life Sciences, and Ph.D. Program in Translational Medicine, College of Life Sciences, National Chung Hsing UniversityDepartment of Life Sciences, and Ph.D. Program in Translational Medicine, College of Life Sciences, National Chung Hsing UniversityDepartment of Medical Biotechnology and Laboratory Science and Division of Biotechnology, College of Medicine, Chang Gung UniversityDepartment of Life Sciences, and Ph.D. Program in Translational Medicine, College of Life Sciences, National Chung Hsing UniversityAbstract Background Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC. Methods To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft. Results An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice. Conclusions Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT.https://doi.org/10.1186/s13287-022-02910-3Amniotic fluid mesenchymal stem cellsPancreatic cancerPANC1 cellsTumorigenicityOrthotopic xenograft |
| spellingShingle | Ying-Cheng Chen Ying-Wei Lan Shiaw-Min Huang Chih-Ching Yen Wei Chen Wan-Ju Wu Theresa Staniczek Kowit-Yu Chong Chuan-Mu Chen Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model Stem Cell Research & Therapy Amniotic fluid mesenchymal stem cells Pancreatic cancer PANC1 cells Tumorigenicity Orthotopic xenograft |
| title | Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model |
| title_full | Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model |
| title_fullStr | Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model |
| title_full_unstemmed | Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model |
| title_short | Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model |
| title_sort | human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model |
| topic | Amniotic fluid mesenchymal stem cells Pancreatic cancer PANC1 cells Tumorigenicity Orthotopic xenograft |
| url | https://doi.org/10.1186/s13287-022-02910-3 |
| work_keys_str_mv | AT yingchengchen humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT yingweilan humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT shiawminhuang humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT chihchingyen humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT weichen humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT wanjuwu humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT theresastaniczek humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT kowityuchong humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel AT chuanmuchen humanamnioticfluidmesenchymalstemcellsattenuatepancreaticcancercellproliferationandtumorgrowthinanorthotopicxenograftmousemodel |