2016 Fiscal Year Final Research Report
Project/Area Number |
15K18396
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Tumor biology
|
Research Institution | Tohoku University |
Principal Investigator |
|
Research Collaborator |
Sasano Hironobu Tohoku University, School of Graduate Medicine, Professor
Kikuchi Kyoko Tohoku University, School of Graduate Medicine, Master Student
Choi Man-Ho Molecular Recognition Research Center, Korea Institute of Science and Technology
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Keywords | Breast Cancer / TNBC / Stroma / Androgens |
Outline of Final Research Achievements |
The tumor microenviroment plays pivitol roles in the initiation and promotion of many malignancies. The goal of this project was to determine if androgen metabolism in the tumor may be impacted by stromal factors. We demonstrated that CAFs increased the expression and activities of major androgen creating enzymes (17BHSD2, 17BHSD5 and 5aR1) in TNBC. To understand the underlying mechanisms cytokine array analysis was used to screen for secreted cytokines from primary human CAFs and these were then cross referenced with cytokines known to impact androgen metabolism. IL-6 and HGF were selected as potential paracrine mediators and their ability to affect androgen metabolism was demonstrated. To generalise from the reductionist context of cell culture CAF markers were examined in a TNBC cohort and found to be significantly correlated with 17BHSD2 and 17BHSD5 expression in TNBC tissues, especially in AR positive cases. This braodly suggests CAF regulation of androgen metabolism in TNBC.
|
Free Research Field |
Breast Cancer
|