Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program
Abstract Epithelial‐to‐mesenchymal transition (EMT) is a recognized eukaryotic cell differentiation program that is also observed in association with invasive tumors. Partial EMT program in carcinomas imparts cancer cells with mesenchymal‐like features and is proposed as essential for metastasis. Pr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2018-10-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201809085 |
| _version_ | 1797283866444038144 |
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| author | Yang Chen Valerie S LeBleu Julienne L Carstens Hikaru Sugimoto Xiaofeng Zheng Shruti Malasi Dieter Saur Raghu Kalluri |
| author_facet | Yang Chen Valerie S LeBleu Julienne L Carstens Hikaru Sugimoto Xiaofeng Zheng Shruti Malasi Dieter Saur Raghu Kalluri |
| author_sort | Yang Chen |
| collection | DOAJ |
| description | Abstract Epithelial‐to‐mesenchymal transition (EMT) is a recognized eukaryotic cell differentiation program that is also observed in association with invasive tumors. Partial EMT program in carcinomas imparts cancer cells with mesenchymal‐like features and is proposed as essential for metastasis. Precise determination of the frequency of partial EMT program in cancer cells in tumors and its functional role in metastases needs unraveling. Here, we employed mesenchymal cell reporter mice driven by αSMA‐Cre and Fsp1‐Cre with genetically engineered mice that develop spontaneous pancreatic ductal adenocarcinoma (PDAC) to monitor partial EMT program. Both αSMA‐ and Fsp1‐Cre‐mediated partial EMT programs were observed in the primary tumors. The established metastases were primarily composed of cancer cells without evidence for a partial EMT program, as assessed by our fate mapping approach. In contrast, metastatic cancer cells exhibiting a partial EMT program were restricted to isolated single cancer cells or micrometastases (3–5 cancer cells). Collectively, our studies identify large metastatic nodules with preserved epithelial phenotype and potentially unravel a novel metastasis program in PDAC. |
| first_indexed | 2024-03-07T17:37:03Z |
| format | Article |
| id | doaj.art-7240628df48e479797a97ac8d277c95a |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:37:03Z |
| publishDate | 2018-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-7240628df48e479797a97ac8d277c95a2024-03-02T16:35:04ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-10-011010n/an/a10.15252/emmm.201809085Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis programYang Chen0Valerie S LeBleu1Julienne L Carstens2Hikaru Sugimoto3Xiaofeng Zheng4Shruti Malasi5Dieter Saur6Raghu Kalluri7Department of Cancer Biology Metastasis Research Center University of Texas MD Anderson Cancer Center Houston TX USADepartment of Cancer Biology Metastasis Research Center University of Texas MD Anderson Cancer Center Houston TX USADepartment of Cancer Biology Metastasis Research Center University of Texas MD Anderson Cancer Center Houston TX USADepartment of Cancer Biology Metastasis Research Center University of Texas MD Anderson Cancer Center Houston TX USADepartment of Cancer Biology Metastasis Research Center University of Texas MD Anderson Cancer Center Houston TX USADepartment of Cancer Biology Metastasis Research Center University of Texas MD Anderson Cancer Center Houston TX USADepartment of Medicine II Klinikum rechts der Isar Technische Universität München München GermanyDepartment of Cancer Biology Metastasis Research Center University of Texas MD Anderson Cancer Center Houston TX USAAbstract Epithelial‐to‐mesenchymal transition (EMT) is a recognized eukaryotic cell differentiation program that is also observed in association with invasive tumors. Partial EMT program in carcinomas imparts cancer cells with mesenchymal‐like features and is proposed as essential for metastasis. Precise determination of the frequency of partial EMT program in cancer cells in tumors and its functional role in metastases needs unraveling. Here, we employed mesenchymal cell reporter mice driven by αSMA‐Cre and Fsp1‐Cre with genetically engineered mice that develop spontaneous pancreatic ductal adenocarcinoma (PDAC) to monitor partial EMT program. Both αSMA‐ and Fsp1‐Cre‐mediated partial EMT programs were observed in the primary tumors. The established metastases were primarily composed of cancer cells without evidence for a partial EMT program, as assessed by our fate mapping approach. In contrast, metastatic cancer cells exhibiting a partial EMT program were restricted to isolated single cancer cells or micrometastases (3–5 cancer cells). Collectively, our studies identify large metastatic nodules with preserved epithelial phenotype and potentially unravel a novel metastasis program in PDAC.https://doi.org/10.15252/emmm.201809085dual‐recombinase systemmetastasismicrometastasispancreatic ductal adenocarcinomapartial epithelial‐to‐mesenchymal transition |
| spellingShingle | Yang Chen Valerie S LeBleu Julienne L Carstens Hikaru Sugimoto Xiaofeng Zheng Shruti Malasi Dieter Saur Raghu Kalluri Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program EMBO Molecular Medicine dual‐recombinase system metastasis micrometastasis pancreatic ductal adenocarcinoma partial epithelial‐to‐mesenchymal transition |
| title | Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program |
| title_full | Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program |
| title_fullStr | Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program |
| title_full_unstemmed | Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program |
| title_short | Dual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program |
| title_sort | dual reporter genetic mouse models of pancreatic cancer identify an epithelial to mesenchymal transition independent metastasis program |
| topic | dual‐recombinase system metastasis micrometastasis pancreatic ductal adenocarcinoma partial epithelial‐to‐mesenchymal transition |
| url | https://doi.org/10.15252/emmm.201809085 |
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