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academies
Cell Science, Stem Cell Research &
Pharmacological Regenerative Medicine
November 29-30, 2017 | Atlanta, USA
Annual Congress on
Adv cel sci tissue cul 2017 | Volume 1 Issue 2
Microenvironment changes cell non-autonomously impose functional phenotypes in epithelial progenitors
causing increased susceptibility to breast cancer
Mark A LaBarge
Beckman Research Institute at City of Hope, USA
M
icroenvironment is a crucial determinant of tissue
and lineage specificity of cells. My lab mainly studies
human mammary epithelia in the context of the aging
process to explore this relationship because more than
75% of women diagnosed with breast cancer each year
are over 55 years of age. We have found that mammary
epithelial cells are unable to maintain strict lineage
specificity with age, which results in deleterious tissue-level
changes making the tissue more susceptible to malignant
transformation. Two processes likely contribute to these
changes and increased cancer incidence the accumulation
of mutations over time, along with numerous changes
to the tissue microenvironment. Microenvironment
changes are essential for allowing expression of malignant
phenotypes in cells and for imposing metastable non-
genetic functional phenotypes in progenitors, which leads
to an epithelium that is more susceptible to transformation.
Microenvironment is defined as the combination of cell-cell,
-ECM and -soluble factor interactions surrounding each cell
in a tissue. These components exchange information with
cells via a combination of physical, chemical and electrical
signals, frequently activating or deactivating the same
pathways triggered by oncogenes. To better understand,
the genesis of age-related states of breast, we developed
cell culture systems that maintain primary human epithelial
cells in ways that maintain the molecular and functional
fingerprint of chronological age and enable robust and
repeated experimentation relevant to
in vivo
. We examine
consequences of the age-related changes by examining
functional responses in bioengineered cell culture substrata
and
in vitro
microtissue assemblies that recapitulate aspects
of
in vivo
tissues. We found that the aging process results
in a continuum of different microenvironments that impose
aging phenotypes that are metastable. We provide evidence
that aging in epithelial progenitors and soma is cell non-
autonomously communicated by microenvironment cues
over at least one cell diameter.
Speaker Biography
Mark A LaBarge is a Cell Biologist with expertise in aging in the context of breast cancer.
He has earned a PhD in Molecular Pharmacology from Stanford and then performed
his Post-doctoral training with Dr. Mina Bissell in the field of Microenvironment Biology.
During that period of training, he has focused on development of novel technologies
that would enable cell-based functional interrogation of tissue microenvironments
(e.g. the combinatorial microenvironment microarray (MEMA)). As a Junior Faculty at
the Lawrence Berkeley National Lab, his lab focused on the role of microenvironment
in age-related breast cancers. He is a recipient of the prestigious Era of Hope Award
for his research in Breast Cancer and is currently a Professor at the Beckman Research
Institute at City of Hope near Los Angeles.
e:
mlabarge@coh.org