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Figure: Mesothelial cell-cell ligation (β-catenin immunostaining using secondary antibodies, magenta shown, nucleus blue shown).
Areas where the ligation combination is interrupted are marked with punctuation instead of continuous staining
.
Cancer cells can invade surrounding tissues
through these weaknesses.
Image credit: University of Pittsburgh Swanson School of Engineering
Most women diagnosed with metastatic ovarian cancer have a survival rate of less than 5 years
.
Researchers at the University of Pittsburgh's Swanson School of Engineering are working to change that
.
Ioannis Zervantonakis, assistant professor of bioengineering at Pitt University, and his team received a four-year, $792,000 grant from the American Cancer Society to understand the biology behind the cellular interactions that lead to ovarian cancer metastasizing to other parts of the body
.
To prevent ovarian cancer from spreading throughout the abdomen, patients undergo a combination of surgery and chemotherapy; However, the outlook remains bleak
.
Zervantonakis explains, "Because ovarian cancer is diagnosed at an advanced stage, patients often do not respond
to chemotherapy.
" "There is an urgent need to understand how ovarian cancer progresses and to develop better bioengineering models to help researchers discover new therapeutic targets
.
"
Ovarian cancer metastasizes
when a tumor is formed by the attachment and growth of mesothelial cells (or cells that cover the outer surface of the visceral inside the abdominal cavity).
In most cases, these attachments lead to complete invasion of host tissue, greatly reducing the patient's chances of
survival after treatment.
Cancer cells secrete IGFBP2, a protein
associated with poor patient outcomes.
When IGFBP2 binds to mesothelial cells, it leads to activation of the SRC pathway, which supports the metastatic process
.
The team believes that by targeting the IGFBP2-SRC interaction between cancer cells and mesothelial cells, ovarian cancer can be prevented from metastasis
.
By developing new three-dimensional models using microfluidic techniques (manipulating fluid movements at the micron scale), the team will be able to study how IGFBP2 production by cancer cells affects mesothelial cell biology and pro-metastasis function
.
Dorota Jazwinska, a graduate student at Pitt University, said: "Most of our experiments will be performed in 3D microfluidic or mouse models, allowing us to really understand what exactly happens
when cells communicate with each other through the production of IGFBP2.
" Dorota Jazwinska is the leader of the experimental work on the project in the
Zervantonakis lab.
Because this project targets mesothelial cells in the abdominal cavity, it will eventually be applicable to other types of cancers
that colonize abdominal organs.
This grant is expected to begin
in January 2023.
In another project on ovarian cancer metastasis, Zervantonakis received $160,000 from the Elsa Pardee Foundation in 2020 to study the role of
macrophages in metastatic ovarian cancer.
