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Biphenotypic Differentiation of Pancreatic Cancer in 3-Dimensional Culture.
Biphenotypic Differentiation of Pancreatic Cancer in 3-Dimensional Culture.
- Source :
-
Pancreas [Pancreas] 2019 Oct; Vol. 48 (9), pp. 1225-1231. - Publication Year :
- 2019
-
Abstract
- Objective: Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the United States. Improved characterized models of PDAC are needed for drug screening.<br />Methods: We grew 4 established pancreatic cancer cell lines in hanging drop cultures to produce spheroids. We also grew organoids from explanted xenografted PDAC and surgically resected primary PDAC. We performed transmission and scanning electron microscopy and compared findings with those of the normal pancreatic duct. We also performed single-cell cloning to determine the potential options for differentiation.<br />Results: Spheroids contained tight junctions and desmosomes but lacked zymogen granules, as expected. The former features were present in normal pancreatic duct but absent from PDAC cell lines grown in standard 2-dimensional culture. Spheroids functionally excluded macromolecules in whole mounts. Cells on the surface of PDAC spheroids were carpeted by microvilli except for rare cells with prominent stereocilia. Carpets of microvilli were also seen in low passage organoids produced from xenografts and surgically resected human PDAC, in addition to normal human pancreatic duct. We performed single-cell cloning and resulting spheroids produced both cell phenotypes at the same approximate ratios as those from bulk cultures.<br />Conclusions: Pancreatic cancer spheroids/organoids are capable of biphenotypic differentiation.
- Subjects :
- Animals
Carcinoma, Pancreatic Ductal ultrastructure
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Desmosomes ultrastructure
Female
Heterografts pathology
Heterografts ultrastructure
Humans
Mice, Nude
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Organoids ultrastructure
Pancreatic Ducts ultrastructure
Pancreatic Neoplasms ultrastructure
Spheroids, Cellular ultrastructure
Tight Junctions ultrastructure
Carcinoma, Pancreatic Ductal pathology
Cell Culture Techniques methods
Organoids pathology
Pancreatic Ducts pathology
Pancreatic Neoplasms pathology
Spheroids, Cellular pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1536-4828
- Volume :
- 48
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Pancreas
- Publication Type :
- Academic Journal
- Accession number :
- 31593010
- Full Text :
- https://doi.org/10.1097/MPA.0000000000001390