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Asian Journal of Biomedical and Pharmaceutical Sciences | Volume 8
March 26-27, 2018 | Orlando, USA
World Summit on
Healthcare & Hospital Management
&
International Conference & Exhibition on
Biologics and Biosimilars
M
etastasis is the primary cause of death in women with
breast cancer. Elevated serum levels of a glycoprotein
known as chitinase-3 like-1 protein (CHI3L1) has been
correlated with poor prognosis and shorter survival of patients
with cancer and inflammatory diseases (Jensen, Johansen, and
Price 2003b). CHI3L1 is known to be expressed in solid tumors
such as breast (Johansen et al. 2003). Inflammation plays a
pivotal role during tumor progression and metastasis. Since
previous studies showed that CHI3L1 modulates inflammation,
we determined the role of CHI3L1 in the context of pre-existing
inflammation and metastasis. Using triple negative model of
breast cancer, we demonstrated that CHI3L1 alters the cellular
composition and inflammatory mediators in the lungs of mice
with pre-existing pulmonary inflammation leading to the
establishment of a metastatic niche. We found that CHI3L1
deficient mice with pre-existing inflammation had decreased
pro-inflammatory mediators, and significant reduction in
tumor volume and metastasis compared to wild type controls.
Pre-existing inflammation and CHI3L1 may be driving the
establishment of a pre-metastatic milieu in the lungs and aiding
in the establishment of metastasis. We show that CHI3L1 levels
are increased at both the “pre-metastatic” and “metastatic
stage” and that tumor cells, splenic, alveolar and interstitial
macrophages, andmyeloid derived population produce CHI3L1.
Thus, CHI3L1 may be one of the more promising prognostic
markers for recurrent breast cancer (Johansen et al. 1995),
metastatic breast cancer (Jensen, Johansen, and Price 2003b)
and advanced breast cancer (Coskun et al. 2007). Therefore,
understanding the role of CHI3L1 in inflammation during tumor
progression could result in targeted therapies for breast cancer
patients.
Methods:
8-12 week-old female BALB/c mice and CHI3L1
knockout mice were used in all studies. Allergic pulmonary
inflammationwas induced inmiceusing anestablished ragweed
sensitization aerosol challengemodel (Shibata et al. 2000). Mice
with established pulmonary inflammation were implanted with
luciferase transfected 4T1mammary tumor cells andmonitored
for tumor progression by
in vivo
imaging. Excised pulmonary
tissue was formalin-fixed and H & E histological analysis was
done to assess metastasis, inflammatory cellular infiltrates and
pulmonary architecture. Flow cytometric analysis of alveolar
and interstitial fluid was performed using antibodies specific.
Results & Discussion:
It is well established that inflammation
within the tumor microenvironment fosters tumor growth
and metastasis. Growth of tumors in 4T1 ragweed mice was
higher compared to the 4T1 saline control mice. Furthermore,
survival in 4T1 ragweed mammary tumor mice was decreased
compared to the 4T1 saline controls.
Speaker Biography
Vijaya Iragavarapu-Charyulu obtained her Ph.D. in Microbiology and Immunology
from University of Miami, Miami, Florida. She is an Associate Professor in Biomedical
Sciences Department where she has been conducting breast cancer research. She is
also invested in the educational mission of College of Medicine. She is a Co-director of
the Fundamentals of Biomedical Sciences course at FAU.
e:
iragavar@health.fau.eduVijaya Iragavarapu-Charyulu
Florida Atlantic University, USA
Chitinase-3-like-1 protein (CHI3L1) expressed during allergic pulmonary inflammation
alters lung microenvironment accelerating breast cancer metastasis