Despite many advances in the battle against cancer, it remains a dreaded diagnosis and a leading cause of death in the United States. The rationale and hope for this proposed research is that any and all knowledge gained in understating how cancer progresses and infiltrates areas of the body brings, not only scientists, but the patients and public closer to achieving their common goal of complete eradication of cancers. The environment surrounding tumors is known to be one of smoldering inflammation and one cell type, known as a tumor-associated macrophage (TAM), prevalent in this environment has been shown to promote many aspects of cancer. TAMs foster tumor progression in multiple ways; they support new tumor blood vessel growth, tumor cell invasion, and even enhance metastasis. A key objective of this proposal is to understand the origin of the cellular signals that stimulateTAM's pro-tumor functions and how these signals act on TAMs. The proposed research is relevant to public health because understanding all of the sources and factors that influence cancer growth and metastasis - be they from the tumor or the body - will ultimately lead to discoveries of how to prevent tumors. Thus, this research is directly relevant to the NIH mission to seek fundamental knowledge that will reduce the burden of illness and lengthen life. The methods employed in order to achieve this goal will be to study tumor models in mice. Tumors will be generated that either do or do not secrete a certain signal, interleukin-4 (IL-4), and thenthese tumors investigated in mice that either do or do not have the ability to produce IL-4. Also, IL-4 and its effects on TAMs both with and without the IL-4 receptor will be studied to help discern how it might play a role in promoting cancer.
The specific aims of this project are to determine the effects of IL-4 secreted from the tumor on tumor growth, metastasis, and TAMs and to understand how IL-4 signals to TAMs to achieve its pro- cancer consequences. It is expected that the impact of the results of this study will be in allowing researchers to target TAMs with future anti-cancer therapy from multiple avenues.

Public Health Relevance

The proposed research is relevant to public health because understanding all of the sources and factors that influence cancer growth and metastasis - be they from the tumor or the body - will ultimately lead to discoveries of how to prevent tumors. Thus; this research is directly relevant to the NIH mission to seek fundamental knowledge that will reduce the burden of illness and lengthen life.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30CA173910-01A1
Application #
8592689
Study Section
Special Emphasis Panel (ZRG1-F09B-P (20))
Program Officer
Damico, Mark W
Project Start
2014-01-14
Project End
2017-01-13
Budget Start
2014-01-14
Budget End
2015-01-13
Support Year
Fiscal Year
2014
Total Cost
$32,738
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109