Spontaneously immortalized mouse mesothelial cells display characteristics of malignant transformation.
OBJECTIVE
Mesotheliomas occur in occult serous cavities after chronic exposure of mesothelial cells to asbestos fibres. Molecular events that contribute to the development of this cancer are therefore not readily accessible for study. We have used in vitro culture systems to study and compare induced and spontaneous transformation events in primary mouse mesothelial cells.


METHODS
Mouse mesothelial cells were cultivated until small populations of proliferating cells emerged from senescing cultures. Spontaneously transformed cultures of cells were characterized and compared to malignantly transformed cells.


RESULTS
Human mesothelial cells had a finite lifespan of 10-15 population doublings when cultured in vitro; mouse mesothelial cells typically exhibit this same pattern. Here, we show that mouse mesothelial cells can be cultured for extended periods and that these cells can transform spontaneously. Lines of spontaneously transformed cells generated in this study are immortal and growth factor-independent. They display the salient characteristic features of transformation, including increased proliferation rate, lack of contact inhibition, aneuploidy and ability to grow in anchorage-independent conditions. A subset of these cell lines developed into tumours in syngeneic mice. Comparative gene expression analysis demonstrated that spontaneously transformed cell lines were more closely related to neoplastic cells than to primary cells.


CONCLUSIONS
These findings have implications for interpretation of in vitro transformation studies, demonstrating broad similarity between spontaneous and induced genetic changes.
Sherwood
A L
AL
National Centre for Asbestos Related Diseases,School of Medicine and Pharmacology, University of Western Australia,Lung Institute of Western Australia,Pathwest, Laboratory Medicine WA, Queen Elizabeth II Medical Centre, andLotterywest State Microarray Facility, Perth, Australia.
Mutsaers
S E
SE
National Centre for Asbestos Related Diseases,School of Medicine and Pharmacology, University of Western Australia,Lung Institute of Western Australia,Pathwest, Laboratory Medicine WA, Queen Elizabeth II Medical Centre, andLotterywest State Microarray Facility, Perth, Australia.
Peeva
V K
VK
National Centre for Asbestos Related Diseases,School of Medicine and Pharmacology, University of Western Australia,Lung Institute of Western Australia,Pathwest, Laboratory Medicine WA, Queen Elizabeth II Medical Centre, andLotterywest State Microarray Facility, Perth, Australia.
Robinson
C
C
National Centre for Asbestos Related Diseases,School of Medicine and Pharmacology, University of Western Australia,Lung Institute of Western Australia,Pathwest, Laboratory Medicine WA, Queen Elizabeth II Medical Centre, andLotterywest State Microarray Facility, Perth, Australia.
DeSilva
C J
CJ
National Centre for Asbestos Related Diseases,School of Medicine and Pharmacology, University of Western Australia,Lung Institute of Western Australia,Pathwest, Laboratory Medicine WA, Queen Elizabeth II Medical Centre, andLotterywest State Microarray Facility, Perth, Australia.
Swanson
N R
NR
National Centre for Asbestos Related Diseases,School of Medicine and Pharmacology, University of Western Australia,Lung Institute of Western Australia,Pathwest, Laboratory Medicine WA, Queen Elizabeth II Medical Centre, andLotterywest State Microarray Facility, Perth, Australia.
Lake
R A
RA
National Centre for Asbestos Related Diseases,School of Medicine and Pharmacology, University of Western Australia,Lung Institute of Western Australia,Pathwest, Laboratory Medicine WA, Queen Elizabeth II Medical Centre, andLotterywest State Microarray Facility, Perth, Australia.
D000818:Animals; D002461:Cell Line, Transformed; D048430:Cell Shape / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology*; D016922:Cellular Senescence / Q000187:drug effects; D004247:DNA / Q000032:analysis; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008654:Mesothelioma / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL
D036341:Intercellular Signaling Peptides and Proteins; D004247:DNA