Eason Hildreth, Ph.D., Assistant Professor, Molecular and Cellular Pathology, has been awarded an American Cancer Society Institutional Research Grant from the O'Neal Comprehensive Cancer Center after submitting his proposal titled, "Investigation of the role of PU.1 in macrophages in breast cancer bone metastasis." The grant is for $40,000 to be used in one year. 

From the O'Neal Comprehensive Cancer website, "The American Cancer Society Institutional Research Grant provides funds to inititate promising new laboratory-based research projects to obtain preliminary results that facilitate successful competition for national research grants." 

Dr. Hildreth's research focuses on the spread of cancer to bone, or bone metastasis. Bone metastasis occurs in 75% of breast cancer patients with metastasis. Once breast cancer cells spread to bone, they increase the activity of cells called osteoclasts (OCs), which are formed from cells called macrophages (MPs), leading to bone loss, pain, and fracture. A protein called PU.1 is essential for both 1) tumor-associated MP (TAM) function and 2) normal MP and OC formation and function. PU.1 acts by controlling the activity of a large number of proteins that also regulate the function of these cell types.

Hildreth will use the American Cancer Society Institutional Research Grant (ACS-IRG) to determine if inhibiting PU.1, specifically in MPs and OCs, can prevent the growth of breast cancer bone metastasis using a mouse model. Many techniques will be used to evaluate the response of both the tumor cells and the TAMs and OCs to PU.1 inhibition. The study will be: 1) measuring the gene and protein response; 2) determining which proteins are interacting with or regulated by PU.1; 3) evaluating by histology all cell types present in the tumors; and 4) imaging the mice to evaluate tumor growth. 

His research proposal suggests that by inhibiting PU.1, many proteins involved in TAM and OC function can be affected. Due to the widespread distribution of MPs normally, and because TAMs make up to 50% of the cells present in breast cancers and their metastasis, targeting PU.1 may have effects on not only bone metastasis, but additionally on the primary breast tumor and metastasis to other organs. 

Findings could be important concerning many tumor types, Hildreth says, but most importantly those that spread to the bone (lung, prostate, thyroid, renal), or those that develop in bone (osteosarcoma, Ewing's sarcoma).