Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Rapamycin inhibits ALDH activity, resistance to oxidative stress, and metastatic potential in murine osteosarcoma cells

Mu, X and Isaac, C and Schott, T and Huard, J and Weiss, K (2013) Rapamycin inhibits ALDH activity, resistance to oxidative stress, and metastatic potential in murine osteosarcoma cells. Sarcoma, 2013. ISSN 1357-714X

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (4MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

Osteosarcoma (OS) is the most common primary malignancy of bone. Mortality is determined by the presence of metastatic disease, but little is known regarding the biochemical events that drive metastases. Two murine OS cell lines, K7M2 and K12, are related but differ significantly in their metastatic potentials: K7M2 is highly metastatic whereas K12 displays much less metastatic potential. Using this experimental system, the mammalian target of rapamycin (mTOR) pathway has been implicated in OS metastasis. We also discovered that aldehyde dehydrogenase (ALDH, a stem cell marker) activity is higher in K7M2 cells than K12 cells. Rapamycin treatment reduces the expression and enzymatic activity of ALDH in K7M2 cells. ALDH inhibition renders these cells more susceptible to apoptotic death when exposed to oxidative stress. Furthermore, rapamycin treatment reduces bone morphogenetic protein-2 (BMP2) and vascular endothelial growth factor (VEGF) gene expression and inhibits K7M2 proliferation, migration, and invasion in vitro. Inhibition of ALDH with disulfiram correlated with decreased mTOR expression and activity. In conclusion, we provide evidence for interaction between mTOR activity, ALDH activity, and metastatic potential in murine OS cells. Our work suggests that mTOR and ALDH are therapeutic targets for the treatment and prevention of OS metastasis. © 2013 Xiaodong Mu et al.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Mu, X
Isaac, C
Schott, Tths33@pitt.eduTHS33
Huard, J
Weiss, Kkrw13@pitt.eduKRW13
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorJaffe, NormanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 1 January 2013
Date Type: Publication
Journal or Publication Title: Sarcoma
Volume: 2013
DOI or Unique Handle: 10.1155/2013/480713
Schools and Programs: School of Medicine > Orthopaedic Surgery
Refereed: Yes
ISSN: 1357-714X
PubMed ID: 23476113
Date Deposited: 31 Mar 2014 15:07
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/20807

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item