3d modeling

Using 3D modeling to stop the spread of cancer

image: Mesothelial cell-cell junctions (β-catenin immunostaining using a secondary antibody shown in magenta and cell nuclei shown in blue). Areas of disrupted junctional assembly are highlighted with punctate staining instead of continuous staining. Cancer cells can squeeze through these weak spots to invade surrounding tissue.
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Credit: University of Pittsburgh Swanson School of Engineering

Most women diagnosed with metastatic ovarian cancer have a survival rate of less than five 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, and his team received $792,000 for four years from the American Cancer Society understand the biology behind the cellular interactions that cause ovarian cancer to metastasize to other parts of the body.

To prevent ovarian cancer from spreading throughout the abdomen, patients are treated with a combination of surgery and chemotherapy; however, the prognosis is still dark.

“Because ovarian cancer is diagnosed at a late stage, patients generally do not respond to chemotherapy,” Zervantonakis explained. “There is an urgent need to understand how ovarian cancer progresses and to develop better bioengineering models that can help researchers discover new therapeutic targets. »

Ovarian cancer becomes metastatic when tumors are formed by attachment and growth on mesothelial cells or cells that line the outer surface of internal organs in the abdominal cavity. In most cases, these attachments result in complete invasion of host tissues, greatly reducing the patient’s chances of survival after treatment.

Cancer cells secrete IGFBP2, a protein associated with a worse prognosis for patients. When IGFBP2 binds to mesothelial cells, it results in activation of the SRC pathway, which supports metastatic progression. The team believe that by targeting this IGFBP2-SRC interaction between cancer cells and mesothelial cells, ovarian cancer metastasis can be halted.

By developing new three-dimensional models using microfluidic technology (a manipulation of fluid movement at the micron scale), the team will be able to study how the production of IGFBP2 by cancer cells impacts mesothelial cell biology and pro -metastatic.

“Most of our experiments will be done in 3D microfluidics or mouse models to give us a good idea of ​​what is really going on when cells talk to each other through the production of IGFBP2,” said graduate student Dorota Jazwinska. of Pitt at the head of the experiment. work at the Zervantonakis Lab on the project.

As this project targets the mesothelial cells of the abdominal cavity, it will eventually be applicable to other types of cancer that colonize the abdominal organs.

The 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.

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