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Ovarian cancer is the fifth cause of cancer-related mortality in women, with an expected 5-year survival rate of only 47%. High-grade serous carcinoma (HGSC), an epithelial cancer phenotype, is the most common malignant ovarian cancer. It is known that the precursors of HGSC originate from secretory epithelial cells within the Fallopian tube, which first develops as serous tubal intraepithelial carcinoma (STIC). Here, we used gene editing by CRISPR-Cas9 to knock out the oncogene  p53  in dog oviductal epithelia cultured in a dynamic microfluidic chip to create an  in vitro  model that recapitulated human STIC. Similar to human STIC, the gene-edited oviduct-on-a-chip, exhibited loss of cell polarization and had reduced ciliation, increased cell atypia and proliferation, with multilayered epithelium, increased  Ki67 ,  PAX8  and  Myc  and decreased  PTEN  and  RB1  mRNA expression. This study provides a biomimetic  in vitro  model to study STIC progression and to identify potential biomarkers for early detection of HGSC.

A dog oviduct-on-a-chip model of serous tubal intraepithelial carcinoma