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dc.contributor.authorLi, Hanchen
dc.contributor.authorFan, Xueli
dc.contributor.authorKovi, Ramesh C.
dc.contributor.authorJo, YunJu
dc.contributor.authorMoquin, Brian
dc.contributor.authorKonz, Richard
dc.contributor.authorStoicov, Calin
dc.contributor.authorKurt-Jones, Evelyn A.
dc.contributor.authorGrossman, Steven R.
dc.contributor.authorLyle, Stephen
dc.contributor.authorRogers, Arlin B.
dc.contributor.authorMontrose, Marshall
dc.contributor.authorHoughton, JeanMarie
dc.date2022-08-11T08:08:57.000
dc.date.accessioned2022-08-23T16:13:51Z
dc.date.available2022-08-23T16:13:51Z
dc.date.issued2007-11-17
dc.date.submitted2008-09-11
dc.identifier.citationCancer Res. 2007 Nov 15;67(22):10889-98. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-07-2665">Link to article on publisher's site</a>
dc.identifier.issn1538-7445 (Electronic)
dc.identifier.doi10.1158/0008-5472.CAN-07-2665
dc.identifier.pmid18006834
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33723
dc.description.abstractAging is the single most common risk factor for cancer. Peripheral and marrow-derived stem cells are long lived and are candidate cells for the cancer-initiating cell. Repeated rounds of replication are likely required for accumulation of the necessary genetic mutations. Based on the facts that mesenchymal stem cells (MSC) transform with higher frequency than other cell types, and tumors in aged C57BL/6 mice are frequently fibrosarcomas, we used a genetically tagged bone marrow (BM) transplant model to show that aged mice develop MSC-derived fibrosarcomas. We further show that, with aging, MSCs spontaneously transform in culture and, when placed into our mouse model, recapitulated the naturally occurring fibrosarcomas of the aged mice with gene expression changes and p53 mutation similar to the in vivo model. Spontaneously transformed MSCs contribute directly to the tumor, tumor vasculature, and tumor adipose tissue, recruit additional host BM-derived cells (BMDC) to the area, and fuse with the host BMDC. Unfused transformed MSCs act as the cancer stem cell and are able to form tumors in successive mice, whereas fusion restores a nonmalignant phenotype. These data suggest that MSCs may play a key role in age-related tumors, and fusion with host cells restores a nonmalignant phenotype, thereby providing a mechanism for regulating tumor cell activity.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18006834&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1158/0008-5472.CAN-07-2665
dc.subjectAdipocytes; Animals; Bone Marrow Transplantation; Cell Line, Transformed; Cell Transformation, Neoplastic; Endothelial Cells; Fibrosarcoma; *Gene Expression Regulation, Neoplastic; *Genes, p53; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; *Point Mutation; Time Factors
dc.subjectCancer Biology
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleSpontaneous expression of embryonic factors and p53 point mutations in aged mesenchymal stem cells: a model of age-related tumorigenesis in mice
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume67
dc.source.issue22
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/386
dc.identifier.contextkey626937
html.description.abstract<p>Aging is the single most common risk factor for cancer. Peripheral and marrow-derived stem cells are long lived and are candidate cells for the cancer-initiating cell. Repeated rounds of replication are likely required for accumulation of the necessary genetic mutations. Based on the facts that mesenchymal stem cells (MSC) transform with higher frequency than other cell types, and tumors in aged C57BL/6 mice are frequently fibrosarcomas, we used a genetically tagged bone marrow (BM) transplant model to show that aged mice develop MSC-derived fibrosarcomas. We further show that, with aging, MSCs spontaneously transform in culture and, when placed into our mouse model, recapitulated the naturally occurring fibrosarcomas of the aged mice with gene expression changes and p53 mutation similar to the in vivo model. Spontaneously transformed MSCs contribute directly to the tumor, tumor vasculature, and tumor adipose tissue, recruit additional host BM-derived cells (BMDC) to the area, and fuse with the host BMDC. Unfused transformed MSCs act as the cancer stem cell and are able to form tumors in successive mice, whereas fusion restores a nonmalignant phenotype. These data suggest that MSCs may play a key role in age-related tumors, and fusion with host cells restores a nonmalignant phenotype, thereby providing a mechanism for regulating tumor cell activity.</p>
dc.identifier.submissionpathgsbs_sp/386
dc.contributor.departmentDepartment of Medicine, Division of Hematology/Oncology
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages10889-98
dc.contributor.studentRamesh C. Kovi; Calin Stoicov


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