Documents in the NTIS Technical Reports collection are the results of federally funded research. They are directly submitted to or collected by NTIS from Federal agencies for permanent accessibility to industry, academia and the public.  Before purchasing from NTIS, you may want to check for free access from (1) the issuing organization's website; (2) the U.S. Government Printing Office's Federal Digital System website http://www.gpo.gov/fdsys; (3) the federal government Internet portal USA.gov; or (4) a web search conducted using a commercial search engine such as http://www.google.com.
Accession Number ADA567696
Title Investigating the Role of Indoleamine 2,3- dioxygenase (IDO) in Breast Cancer Metastasis.
Publication Date Sep 2012
Media Count 47p
Personal Author C. Smith
Abstract First identified as a mediator of acquired immune tolerance of the foreign fetus from maternal immunity, the tryptophan-catabolizing enzyme IDO (indoleamine 2,3-dioxygenase) has since been implicated in tumor escape from the host immune system. Primary tumor growth of the metastatic 4T1 breast cancer model was unaffected in the IDO-deficient mice, however, survival was significantly improved. This provided a basis for our studies exploring the importance of IDO in the metastatic site of the lung. Elevation of the inflammatory cytokine IL-6 was associated with tumor outgrowth in the lungs but was greatly attenuated with the loss of IDO, consistent with the in vitro demonstration that IDO activity markedly potentiates IL-6 production. MDSCs (myeloid derived suppressor cells) exhibited reduced T-cell suppressive activity when isolated from tumor-bearing, IDO-deficient animals that could be rescued by ectopic production of IL-6 in the tumor. IL-6 production could likewise reverse the pulmonary metastasis resistance exhibited by IDO-deficient mice. Interestingly, while there is a clear role of the immune system in lung tumor and metastatic outgrowth, IDO-deficient mice appear to have reduced vascularization in the lung which may partly contribute to reduced tumor formation. Together, these findings genetically validate IDO as a therapeutic target in the settings of metastasis and establish the importance of IDO as a driver of IL-6 production and MDSC function. Furthermore, the correlation of IDO to angiogenesis may be a new insight into the role of this enzyme in cancer.
Keywords 3-dioxygenase
4t1
Breast cancer
Cytokines
Il-6
Indoleamine 2
Lung cancer
Metastasis
Myeloid derived suppressor cells
Pregnancy
Tolerances(Physiology)
Vascularization


 
Source Agency Non Paid ADAS
NTIS Subject Category 57A - Anatomy
57S - Physiology
57E - Clinical Medicine
Corporate Author Lankenau Hospital Research Inst., Philadelphia, PA.
Document Type Technical report
Title Note Final rept. 1 Sep 2009-31 Aug 2012.
NTIS Issue Number 1309
Contract Number W81XWH-09-1-0667

Science and Technology Highlights

See a sampling of the latest scientific, technical and engineering information from NTIS in the NTIS Technical Reports Newsletter

Acrobat Reader Mobile    Acrobat Reader