R. Daniel Bonfil
R. Daniel Bonfil, Ph.D.
540 E. Canfield
9105 Scott Hall
Detroit, MI 48201
•Prostate cancer bone metastasis
•Roles of matrix metalloproteinases in invasion, angiogenesis, and tumor progression in prostate cancer
•Stem cell factor/c-kit axis in prostate cancer bone metastasis
•Circulating tumor cells
In prostate cancer (PCa), the development of bone metastasis indicates incurable disease, and the subsequent development of metastatic castrate resistant (mCR) PCa inevitably follows. The molecular mechanisms by which disseminated tumor cells convert into bone metastasis are unknown. In an effort to identify potential mechanisms involved, our lab focused during the last years on the study of tumor-associated Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) and its contribution to PCa bone metastasis. We were the first ones in demonstrating that MT1-MMP is highly expressed in clinical specimens of PCa bone metastasis, and that tumor-associated MT1-MMP facilitates intraosseous tumor growth and osteolysis using experimental models. Moreover, we discovered that this protease is involved in ectodomain shedding of membrane-anchored receptor activator of nuclear factor kB ligand (RANKL) expressed by PCa cells, resulting not only in paracrine activation of pre-osteoclasts but in autocrine stimulation of PCa cell motility. We are also investigating the role played by the receptor tyrosine kinase c-kit in intraosseous expansion of PCa within the bone microenvironment. We demonstrated an association between c-kit expression by epithelial prostate cells and malignant progression in archival samples, and demonstrated the induction of c-kit expression by the bone microenviroment in PCa cells otherwise c-kit negative. Another area of research interest involves circulating tumor cells, with special emphasis on exploring relationships between gene expression profile of CTCs and survival and response to therapy in mCRPCa patients.
Dzinic SH, Bernardo MM, Li X, Fernandez-Valdivia R, Ho YS, Mi QS, Bandyopadhyay S, Lonardo F, Vranic S, Oliveira D, Bonfil RD, Dyson G, Chen K, Omerovic A, Sheng X, Han X, Wu D, Bi X, Cabaravdic D, Jakupovic U, Wahba M, Pang A, Harajli D, Sakr W, Sheng S. An essential role of maspin in embryogenesis and tumor suppression. Cancer Res. 2016 Dec 6. [Epub ahead of print]
Cho WJ, Oliveira DS, Najy AJ, Mainetti LE, Aoun HD, Cher ML, Heath E, Kim HR, Bonfil RD. Gene expression analysis of bone metastasis and circulating tumor cells from metastatic castrate-resistant prostate cancer patients. J Transl Med. 2016;14:72.
Oliveira DS, Dzinic S, Bonfil AI, Saliganan AD, Sheng S, Bonfil RD. The mouse prostate: a basic anatomical and histological guideline. Bosn J Basic Med Sci. 2016;16:8-13.
Mainetti LE, Zhe X, Diedrich J, Saliganan AD, Cho WJ, Cher ML, Heath E, Fridman R, Kim HR, Bonfil RD. Bone-induced c-kit expression in prostate cancer: a driver of intraosseous tumor growth. Int J Cancer. 2015;136:11-20.
Education and Training:
MSc (1981), PhD (1986): University of Buenos Aires, Argentina
Post-Doc (1986-1988): Fox Chase Cancer Center, Philadelphia, Pennsylvania
Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7240 Principles of Cancer Therapy
CB7700 Recent Developments in Cancer Biology