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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Friday, January 31, 2025
Ovarian cancer cells appear to actively sabotage the fitness of neighboring host cells by releasing long noncoding RNA that targets a gene called Flower, according to a recent preclinical study published in Nature Biotechnology. Pretreating mice with a humanized monoclonal antibody to the Flower protein slowed the development of lesions, even in the presence of aggressive tumor cells. The research was conducted by Esha Madan, PhD; Rajan Gogna, PhD, both of Virginia Commonwealth University, Richmond, Virginia; and colleagues.
The human Flower gene can result in two different protein types depending on gene splicing: Flower Lose and Flower Win. Cells expressing Flower Lose are eliminated if their neighboring cells express Flower Win. Previous research established that human tumors express increased levels of Flower Win, whereas their surrounding host cells expressed higher levels of Flower Lose, but whether this was caused by the tumor was unknown.
In high-grade serous ovarian cancer (HGSOC), the researchers found that cancer cells release a long noncoding RNA called Tu-Stroma that controls splicing in the Flower gene in neighboring host cells. The long noncoding RNA appears to cause these nearby host cells to express Flower Lose, which decreases their fitness.
In a group of 99 patients with HGSOC, those with higher expression of Tu-Stroma and Flower Lose had lower median survival rates than patients with a lower expression of these genes. The researchers confirmed these results in an independent group of 296 patients with HGSOC.
Subsequently, the researchers constructed a humanized monoclonal antibody that targets the Flower protein. When they pretreated mice with this antibody and then 2 weeks later injected the mice with HGSOC, they found reduced cancer growth, reduced metastasis, and increased survival compared with untreated mice or mice treated with the empty vehicle used for antibody delivery. Pretreatment with the antibody was capable of protecting organs from developing lesions even when the mice were injected with aggressive tumor cells.
Disclosure: The study authors reported no conflicts of interest.
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