Vol 31, Part I - forums.sou.edu • Index page - Southern Oregon ...

ABSTRACTS – Contributed Oral Papers
phenotype. Important epithelial markers include E-cadherin
and α-catenin, which are both cell-cell adhesion proteins that
are down regulated in the presence of inflammatory cytokines.
Mesenchymal markers such as vimentin, fibronectin,
and N-cadherin, which are important for cellular flexibility,
are upregulated in the presence of inflammatory cytokines.
Downregulation of epithelial markers and an upregulation of
mesenchymal markers in conjunction with a change in cellular
morphology is a hallmark for epithelial-mesenchymal
transition (EMT). Once a cell transitions to a mesenchymal
phenotype it is able to metastasize to different locations in
the body. After extravasation, cells arrive at their secondary
location where they will undergo mesenchymal-epithelial
transition (MET), which is a reverse EMT to establish a secondary
tumor. This metastatic process presents major challenges
for the treatment of breast cancer. Targeting inflammatory
cytokines that promote EMT would be beneficial in
preventing metastasis.
Funding provided by NIH R15 NIH R15CA137510; INBRE (NIH/NCRR)
NIH/NCRR P20RR016454 & P20GM103408; Komen KG100513; ACS
RSG-09-276-01-CSM.
127 The Role of Autophagy in the Development and Treatment
of Colon Cancer, TOM DONNDELINGER*
and JOELLA SKYLES (Department of Pathology, St.
Alphonsus Hospital, 1512 12 th Ave Rd, Nampa, ID 83686;
tdonndel@bi-biomics.com).
After implementation of updates to the 120-year-old
biopsy process, newly achieved tissue detail revealed a complex
system of cell recycling in the intestinal crypts of the
colon. This autophagic system involves the migration of
cells up the side of the crypt and, rather than being shed, they
enter autophagocytosis. After entering autophagocytosis, an
autophagic vacuole forms in the cell after which it migrates
through a pore in the basement membrane where the vacuole
can then be enveloped and digested by the macrophage.
A healthy colon is able to dissemble aged cells into amino
acids, peptides, and other materials to be recycled for use in
other cells.
When a signaling error occurs which prevents the
migration of cells through the basement membrane during
autophagy, the cell cannot be effectively recycled but instead
remains at the top of the intestinal crypts where it then continues
the autophagic system. The resumption of autophagy
causes replication of a dysfunctional cell and the development
of an adenomatus polyp with pre-cancerous features
such as an enlarged nucleus...Ultimately, it is the disruption
in the cycle of autophagy that acts as the first step in the
development in colon cancer.
By understanding the role autophagy plays in early stage
colon cancer, new treatment alternatives emerge that involve
the manipulation of this autophagic system. Clinical trials
could then focus on drugs, such as chloroquine, designed
to silence the autophagic signaling in dysfunctional cells in
effort to halt the persistence of select abnormal cells.
128 Quantitative Evaluation of the Inductive Effects of
OSM-Signaling on Breast Cancer Metastasis to Bone,
JIM MOSELHY 1 *, KEN TAWARA 1 , JEFF RED-
SHAW 1 , CELESTE BOLIN 1 , ROBIN ANDERSON 2 ,
and CHERYL L JORCYK 1 ( 1 Department of Biological
Sciences, Boise State University, Boise, ID 83725; 2 Peter
MacCallum Cancer Centre, Melbourne, Victoria, Australia,
8006; jimmoselhy@boisestate.edu).
In humans, bone is the most frequent site of metastasis
of breast cancer affecting approximately 75% of patients
with the disease. To better understand the underlying pathological
mechanisms driving breast cancer progression and
metastasis to bone, we have sought to shed light on the role
of signaling via the IL-6 family pro-inflammatory cytokine,
oncostatin M (OSM) and its receptor (OSMRb). We have
developed a mouse model of bone-metastasizing breast
cancer using the bone-homing murine breast cancer cell
line 4T1.2. Stably transfected 4T1.2 cell lines with knockdown
expression of OSM (4T1.2-OSM) and the respective
vector-transfected control 4T1.2-lacZ were injected into
the 4th mammary fat pad of Balb/c mice. Spines were harvested
from sacrificed animals and genomic DNA extracts
prepared. Real-time quantitative polymerase chain-reaction
(qPCR) was performed on the extracts using primers specific
for neomycin (Neo) as the reporter gene and vimentin (Vim)
as the housekeeping gene. Bone metastasis was assessed by
the relative tumor burden using the comparative (DDCt)
method referenced against genomic DNA derived from the
parental cell lines. To further examine the effects of OSMsignaling
on breast cancer metastasis to bone, a tetracyclineinducible
lentivirus vector was prepared incorporating mouse
OSM (mOSM) gene in order to test the effects of temporal
modulation of OSM levels on bone metastasis. Results from
our experiments will help to establish the impact of tumorderived
OSM on breast cancer metastasis to bone.
Funding for this project is gratefully acknowledged under the following
grants: American Cancer Society: ACS RSG-09-276-01-CSM; Susan G.
Komen for the Cure: KG100513; National Institute for Health Sciences:
NIH/NCRR P20RR016454.
129 A Molecular Mechanism for Metastatic Breast Cancer-Mediated
Bone Destruction, KEN TAWARA* and
CHERYL JORCYK (Department of biological sciences,
Boise State University, 1910 University Drive, Boise, ID
83725; kentawara@boisestate.edu, cjorcyk@boisestate.edu).
One of the end-stage clinical manifestations of metastatic
breast cancer is osteolytic bone metastases that leads
to pathologic fractures, spinal cord compression, intense
pain, reduced mobility, and complications associated with
hypercalcemia. In normal bone there is a balance of activity
between the cells that make bone, osteoblasts; and the cells
that degrade bone, osteoclasts. However, metastases to bone
disrupt this balance, which result in uncontrolled osteoclast
activity and bone destruction. Palliative therapies such as
bisphosphonates slow down bone degradation by inhibiting
85