Cancer-Prone Cell States of the Fallopian Tubal Epithelium

The most common type of ovarian cancer is also the most aggressive: high-grade serous carcinoma (HGSC). Early-stage HGSC often has no symptoms, and in most cases, tumors have already metastasized by the time HGSC is diagnosed.

Recent studies have established that a significant portion of HGSC arises from the epithelial tissues lining the fallopian tubes, also called the tubal epithelium. A team of Cornell researchers led by Alexander Yu. Nikitin, Biomedical Sciences, is investigating various cell types and their differentiation states present within the tubal epithelium. The research is aimed at testing if cancer-susceptible cell states are determined by levels of epithelial damage and changes in stroma, the connective tissue underlying tubal epithelium.

Preliminary studies by the Nikitin lab suggest that changes in stroma begin to coevolve with mutant epithelial cells before the structural, morphological changes characteristic of HGSC can be detected. With this project, researchers will attempt to 1) establish the role of specific epithelial cell states in normal homeostatic regeneration of epithelial tissues as well as in post-traumatic regeneration following cellular damage; 2) determine how damage affects the cancer susceptibility of distinct populations of epithelial cells; and 3) identify and characterize the dynamics of epithelial and stromal cell lineages during early stages of malignancy.

This project will establish the roles of epithelial damage and stromal changes in determining cancer-prone cell states of the tubal epithelium. Findings will provide a basis for identifying unique biomarkers for HGSC that could lead to earlier detection and new modes of treatment.

NIH Award Number: 1R01CA260115-01

Cornell Researchers

Funding Received

$2.1 Million spanning 5 years