# 11α-hydroxyprogesterone dampens lung metastasis via EMT modulation in PyMT-induced breast cancer murine model

## TL;DR

11α-hydroxyprogesterone reduces lung metastasis in a breast cancer mouse model by modulating epithelial-mesenchymal transition.

## Contribution

11α-hydroxyprogesterone's novel role in suppressing metastasis via EMT modulation is demonstrated in a PyMT-induced breast cancer model.

## Key findings

- 11α-OHP significantly reduced lung metastasis in MMTV-PyMT mice.
- 11α-OHP increased epithelial cell adhesion proteins and decreased FAK in lung tissues.
- 11α-OHP inhibited cell motility and invasiveness in MDA-MB-231 cells in vitro.

## Abstract

Despite the availability of various therapeutic strategies, the prognosis for patients with metastatic breast cancer remains poor. Epithelial-mesenchymal transition (EMT) is a critical mechanism driving metastasis in breast cancer, enabling tumor cells to lose epithelial characteristics and acquire enhanced motility and invasiveness.

This study investigates the role of 11alpha-hydroxyprogesterone (11α-OHP), a steroid hormone with an incompletely understood biosynthesis and metabolic pathway, in regulating lung metastasis in breast cancer. Using the MMTV-PyMT FVB mouse model, which spontaneously develops breast tumors we administered 11α-OHP for five weeks starting at 10 weeks of age. At 15 weeks, histological analysis revealed a significant reduction in lung metastasis in 11α-OHP-treated mice compared to controls, with notably smaller metastatic tumor areas in the lungs. Additionally, treated mice exhibited increased expression of epithelial cell adhesion proteins and decreased levels of focal adhesion kinase (FAK) in lung tissues. In vitro experiments using MDA-MB-231 cells corroborated these findings, showing that 11α-OHP significantly inhibited cell motility and invasiveness in scratch wound, transwell migration, and invasion assays. Notably, 11α-OHP did not significantly alter primary tumor growth in the MMTV-PyMT model.

These findings suggest that 11α-OHP may suppress breast cancer metastasis by modulating EMT, highlighting its potential as a therapeutic target for preventing metastatic progression.

The online version contains supplementary material available at 10.1186/s42826-025-00259-1.