An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer
Metastasis is the primary cause of death in patients with colorectal cancer (CRC), urging the need for preclinical models that recapitulate the metastatic process at the individual patient level. We used an orthotopic patient-derived xenograft (PDX) obtained through the direct implantation of freshl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.869485/full |
| _version_ | 1811342710500491264 |
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| author | Maria Laura De Angelis Federica Francescangeli Chiara Nicolazzo Eljona Xhelili Filippo La Torre Lidia Colace Alessandro Bruselles Daniele Macchia Sara Vitale Paola Gazzaniga Marta Baiocchi Ann Zeuner |
| author_facet | Maria Laura De Angelis Federica Francescangeli Chiara Nicolazzo Eljona Xhelili Filippo La Torre Lidia Colace Alessandro Bruselles Daniele Macchia Sara Vitale Paola Gazzaniga Marta Baiocchi Ann Zeuner |
| author_sort | Maria Laura De Angelis |
| collection | DOAJ |
| description | Metastasis is the primary cause of death in patients with colorectal cancer (CRC), urging the need for preclinical models that recapitulate the metastatic process at the individual patient level. We used an orthotopic patient-derived xenograft (PDX) obtained through the direct implantation of freshly dissociated CRC cells in the colon of immunocompromised mice to model the metastatic process. Ortho-PDX engraftment was associated to a specific set of molecular features of the parental tumor, such as epithelial-to-mesenchymal transition (EMT), TGF-β pathway activation, increased expression of stemness-associated factors and higher numbers of circulating tumor cells (CTCs) clusters expressing the metastatic marker CD44v6. A parallel analysis of orthotopic/metastatic xenografts and organoids showed that tumor cells underwent mesenchymal-to-epithelial transition at the metastatic site and that metastasis-derived organoids had increased chemotherapy resistance. These observations support the usefulness of ortho-PDX as a preclinical model to study metastasis-related features and provide preliminary evidence that EMT/stemness properties of primary colorectal tumors may be crucial for orthotopic tumor engraftment. |
| first_indexed | 2024-04-13T19:16:47Z |
| format | Article |
| id | doaj.art-625f39741d3243fcbdc5ddf89a79394b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T19:16:47Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-625f39741d3243fcbdc5ddf89a79394b2022-12-22T02:33:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.869485869485An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal CancerMaria Laura De Angelis0Federica Francescangeli1Chiara Nicolazzo2Eljona Xhelili3Filippo La Torre4Lidia Colace5Alessandro Bruselles6Daniele Macchia7Sara Vitale8Paola Gazzaniga9Marta Baiocchi10Ann Zeuner11Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyDepartment of Molecular Medicine, Liquid Biopsy Unit, Sapienza University, Rome, ItalySurgical Sciences and Emergency Department, Policlinico Umberto I/Sapienza University of Rome, Rome, ItalySurgical Sciences and Emergency Department, Policlinico Umberto I/Sapienza University of Rome, Rome, ItalyDepartment of Surgical Sciences, Policlinico Umberto I/Sapienza University of Rome, Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyCenter of Animal research and Welfare, Istituto Superiore di Sanità, Rome, ItalyDepartment of Medicine and Traslational Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyDepartment of Molecular Medicine, Liquid Biopsy Unit, Sapienza University, Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyMetastasis is the primary cause of death in patients with colorectal cancer (CRC), urging the need for preclinical models that recapitulate the metastatic process at the individual patient level. We used an orthotopic patient-derived xenograft (PDX) obtained through the direct implantation of freshly dissociated CRC cells in the colon of immunocompromised mice to model the metastatic process. Ortho-PDX engraftment was associated to a specific set of molecular features of the parental tumor, such as epithelial-to-mesenchymal transition (EMT), TGF-β pathway activation, increased expression of stemness-associated factors and higher numbers of circulating tumor cells (CTCs) clusters expressing the metastatic marker CD44v6. A parallel analysis of orthotopic/metastatic xenografts and organoids showed that tumor cells underwent mesenchymal-to-epithelial transition at the metastatic site and that metastasis-derived organoids had increased chemotherapy resistance. These observations support the usefulness of ortho-PDX as a preclinical model to study metastasis-related features and provide preliminary evidence that EMT/stemness properties of primary colorectal tumors may be crucial for orthotopic tumor engraftment.https://www.frontiersin.org/articles/10.3389/fonc.2022.869485/fullpatient-derived xenograft (PDX)colorectal cancer (CRC)metastasisepithelial-to-mesenchymal transition (EMT)organoids |
| spellingShingle | Maria Laura De Angelis Federica Francescangeli Chiara Nicolazzo Eljona Xhelili Filippo La Torre Lidia Colace Alessandro Bruselles Daniele Macchia Sara Vitale Paola Gazzaniga Marta Baiocchi Ann Zeuner An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer Frontiers in Oncology patient-derived xenograft (PDX) colorectal cancer (CRC) metastasis epithelial-to-mesenchymal transition (EMT) organoids |
| title | An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer |
| title_full | An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer |
| title_fullStr | An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer |
| title_full_unstemmed | An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer |
| title_short | An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer |
| title_sort | orthotopic patient derived xenograft pdx model allows the analysis of metastasis associated features in colorectal cancer |
| topic | patient-derived xenograft (PDX) colorectal cancer (CRC) metastasis epithelial-to-mesenchymal transition (EMT) organoids |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.869485/full |
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