2015 Fiscal Year Research-status Report
| Project/Area Number |
15K18396
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
MCNAMARA K.M 東北大学, 医学(系)研究科(研究院), 助教 (60721389)
|
|---|
| Project Period (FY) |
2015-04-01 – 2017-03-31
|
| Keywords | Stroma / TNBC / Androgen / Glucocorticoids |
|---|
| Outline of Annual Research Achievements |
To date this research has been going well, despite some initial setbacks that forced changes to the details of the experimental design. In examining patient samples we have looked at the two stromal markers that identify cancer associated fibroblasts (CD and alpha SMA) in a cohort of around 80 triple negative breast cancer patients, and are in the process of expanding this cohort by around an additional 50 patients. We then correlated the expression of these factors with the expression of androgen receptor and its associated enzymes to try and determine if stromal alterations govern changes in androgen signalling in this breast cancer subtype. In parallel we have been examining the interactions of AR and other nuclear receptors in the stromal as well as the epithelial compartments, as well as the presence of other indicators of altered cellular metabolism.
In parallel we have managed to characterize the cytokines secreted by two different patients stromal fibroblasts in response to two separate triple negative cell lines, to examine if the co-culture affects androgen metabolism and untangle underlying mechanisms.
On the strength of this data we are in the process of preparing the first manuscript to come from this work.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The experiments are going well. The one issue that forced the greatest shift in our experimental design was that the fibroblasts we obtained from triple negative breast cancers did not grow well in culture. Until we can obtain more such precious material we have chosen to progress with the project by the use of fibroblasts obtained from other subtypes of breast cancers, and to focus on the changes affected by TNBC epithelial cell lines on these fibroblasts. It is a similar discovery approach to the initial experimental plan and has allowed to smooth progression of the experiments.
|
| Strategy for Future Research Activity |
We are currently preparing the first manuscript that will describe the initial findings concerning androgen metabolism and stromal signalling in triple negative breast cancers. As we have some interesting findings we will follow these to try and understand in detail the mechanistic underpinnings of these interactions. Beyond that the initial cytokine screen that we used revealed many interesting changes in cytokine expression profiles that we have not yet pursued.
Beyond this research in the field in the last year has provided support for interaction of androgen and other nuclear receptors in altering cancer phenotype. Therefore intend to incorporate and examination of how these interactions may modulate stromal-epithelial cross talk in order to determine overall biological behavior.
Finally we hope that some primary triple negative tumor tissue may yield viable triple negative derived fibroblasts allowing us to use the data generated from the experiments above to directly asses any differences between TNBC fibroblasts and others.
|
Research Products
(3 results)
