Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.
Publication Title
Nature biotechnology
Document Type
Article
Publication Date
12-9-2024
Keywords
oregon; chiles
Abstract
Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.
Area of Special Interest
Cancer
Area of Special Interest
Women & Children
Specialty/Research Institute
Oncology
Specialty/Research Institute
Obstetrics & Gynecology
Specialty/Research Institute
Earle A. Chiles Research Institute
DOI
10.1038/s41587-024-02453-3
