GSBS Student Publications
GSBS Program
Cancer Biology
Publication Date
2010-8
UMMS Affiliation
Department of Cancer Biology;Department of Medicine, Division of Gastroenterology;Department of Medicine, Division of Hematology and Oncology; Graduate School of Biomedical Sciences
Document Type
Article
Disciplines
Cancer Biology | Oncology
Abstract
Neoplastic epithelia may remain dormant and clinically unapparent in human patients for decades. Multiple risk factors including mutations in tumor cells or the stromal cells may affect the switch from dormancy to malignancy. Gene mutations, including p53 mutations, within the stroma of tumors are associated with a worse clinical prognosis; however, it is not known if these stromal mutations can promote tumors in genetically at-risk tissue. To address this question, Apc(Min/+) and Apc(Min/+) Rag2(-/-) mice, which have a predilection to mammary carcinoma (as well as wild-type (wt) mice), received mesenchymal stem cells (MSC) with mutant p53 (p53MSC) transferred via tail vein injection. In the wt mouse, p53MSC circulated in the periphery and homed to the marrow cavity where they could be recovered up to a year later without apparent effect on the health of the mouse. No mammary tumors were found. However, in mice carrying the Apc(Min/+) mutation, p53MSC homed to mammary tissue and significantly increased the incidence of mammary carcinoma. Tumor necrosis factor (TNF)-alpha-dependent factors elaborated from mesenchymal cells converted quiescent epithelia into clinically apparent disease. The increased cancer phenotype was completely preventable with neutralization of TNF-alpha or by transfer of CD4(+) regulatory T cells from immune competent donors, demonstrating that immune competency to regulate inflammation was sufficient to maintain neoplastic dormancy even in the presence of oncogenic epithelial and stromal mutations. The significant synergy between host immunity and mesenchymal cells identified here may restructure treatments to restore an anticancer microenvironment.
DOI of Published Version
10.1089/scd.2009.0439
Source
Stem Cells Dev. 2010 Aug;19(8):1153-66. doi: 10.1089/scd.2009.0439. Link to article on publisher's site
Journal/Book/Conference Title
Stem cells and development
Related Resources
PubMed ID
20199238
Repository Citation
Houghton, JeanMarie; Li, Hanchen; Fan, Xueli; Liu, Yingwang; Liu, Jian Hua; Rao, Varada P.; Poutahidis, Theofilos; Taylor, Christine L.; Jackson, Erin A.; Hewes, Christine; Lyle, Stephen; Cerny, Anna M.; Bowen, Glennice N.; Cerny, Jan; Moore, Nathan F.; Kurt-Jones, Evelyn A.; and Erdman, Susan E., "Mutations in bone marrow-derived stromal stem cells unmask latent malignancy" (2010). GSBS Student Publications. 1807.
https://escholarship.umassmed.edu/gsbs_sp/1807