Neurotrophins and their effects on breast cancer cell proliferation and migration
Abstract
Cancer is a large health issue in all parts of the world. In the United States alone, approximately 1 in 4 deaths are cancer related. Breast cancer is a particularly prevalent form, accounting for a little over 14 percent of all cancer incidence. The largest obstacle to overcome for breast cancer morbidity is metastasis. Over 90 percent of all breast cancer related deaths are due to metastasis. Because metastasis is a complex, multi-step process, it is difficult to treat. A recent observation in the Kirshner lab has revealed a type of phenotypic plasticity, where migratory cancer cells have a neuronal-like morphology with multiple axon-like projections. This observation has led to an interest in the characteristics of these cells and how they relate to metastasis. One of the characteristics is receptivity to neurotrophins, which are neuronal growth factors. We have shown that MCF10CA1a cells, a malignant progression of the MCF10 series, do express three neuronal receptors, TrkA, TrkB, and p75NTR in both 2D and 3D cell culture. Addition of neurotrophins, NGF, BDNF, and NT 4/5 increase proliferation between 24 and 72 hours of treatment in 2D cell culture. Further, addition of NGF and NT 4/5 act as a chemoattractant to these cells, increasing their migration towards the neurotrophin. From these results we conclude that neurotrophins do have an effect on the proliferation and migration of breast cancer cells. This could serve as a therapeutic target for future treatment of breast cancer and breast cancer metastasis.
Degree
M.S.
Advisors
Kirshner, Purdue University.
Subject Area
Molecular biology|Cellular biology|Oncology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.