Senny Wong, a graduate student in the Department of Biochemistry, is studying
breast cancer metastasis in Dr. Iain Buxton’s lab. She has been researching on how
purinergic mechanisms influence breast cancer metastasis. The fundamental
protein of interest is a secreted factor that has been shown to be released by breast
cancer cells but not normal breast cells. This factor has a role in elevating nucleotide
pools (particularly of interest is ATP) in the extracellular microenvironment. We
propose this elevation of ATP near the blood vessels can contribute to the
generation of new blood vessel formation and a pathway for breast cancer cells to
escape to distant regions of the body. Understanding these mechanisms can be
utilized for pharmacologic methods to target and treat breast cancer. She is
currently interested in exosomes, small lipid vesicles secreted from cells, as
biomarker carriers for the diagnostics of breast cancer.
Senny has received her B.Sc. in Biochemistry at the University of Nevada, Reno.
Senny has mentored students; Katie Speirs and Suzann Duan. Below are their
achievements and current statuses.
Undergraduates
Katie Speirs (2012-2014)
Achievements:
GURA 2012-13: Preventing Metastases of Human Breast Cancer Cells in an
Immunocompromized Mouse Model of Human Cancer
Summer INBRE 2013: Development and Optimization of a Luciferin-Luciferase
Activity Assay for the Detection of Nucleoside Diphosphate Kinase
GURA 2013-14: Optimization of Detection Methods for Nucleotide Diphosphate Kinase
in Human Breast Cancer Tissues
Current status: Accepted for medical school
Suzaan Duan (2013-2014)
Current status: Accepted in the CMPP graduate program
Breast cancer research
Breast cancer is a heterogeneous disease comprised of many dysregulated pathways
and is the most common cancer diagnosed in women. Within the developed world,
breast cancer patients usually succumb due to metastasis of the cancer and not from
the primary tumor. This demonstrates the importance of understanding and
treating metastasis. There is strong evidence that breast cancer metastasizes away
from the breast early on during tumor development. Cells at distant sites can remain
dormant for an extended period of time despite loco-regional treatment including
surgical removal of the primary tumor. These secondary metastases can then grow
large enough to attract their own blood supply by a process known as angiogenesis.
Several studies have shown that nucleoside diphosphate kinase (NM23 or NDPK)
may have a pathological role in cancer. NDPK-A was detected in the serum of
patients diagnosed from lymphoma, neuroblastoma, and melanoma. Our lab has
shown that NDPK-A and B is elaborated outside breast cancer cells. NDPK has been
shown to promote cell migration, proliferation, and tumor-mediated angiogenesis
that would support metastasis. The functional role of NDPK generates extracellular
ATP from ADP thus elevating ATP/ADP levels. Nucleotide release has been
established to have signaling roles in many organ systems. Extracellular ATP can
activate purinergic (P2Y) receptors leading to transactivation of vascular
endothelial growth factor receptor (VEGFR) on endothelial cells, which promotes
angiogenesis, tubulogenesis, and cell proliferation. This activation can occur in the
absence of VEGF. Another role for ATP is the dilation of arterial vessels. Activation of
P2Y receptors can release nitric oxide, prostaglandins, and more ATP from
endothelial cells leading to vasodilation in arterioles. Stimulating P2Y on endothelial
cells may also cause cell contraction leading to vascular permeability to support
cancer cell intravasation and extravasation for migrating to secondary sites in the
body. Thus, NDPK provides a means for the cancer cell to travel to distant sites in
the body and propagate during metastasis.