Short Peptides Emerge as Potential Blockers of Breast Cancer Metastasis

In a groundbreaking study published in the April 2025 edition of the *British Journal of Pharmacology*, researchers from Hiroshima University have identified a novel mechanism by which short peptides could impede the metastasis of breast cancer cells. This research addresses a significant challenge in oncology: while surgical interventions can excise primary tumors, they often fail to eliminate disseminated cancer cells that can lead to recurrence and further spread.

The study, led by Dr. Satoshi Asano, Assistant Professor in the Department of Cellular and Molecular Pharmacology at Hiroshima University, focuses on the vasoactive intestinal peptide receptor-2 (VIPR2). This receptor is known to play multiple roles in human physiology, including regulation of circadian rhythms and immune responses. However, in breast cancer, an overexpression of VIPR2 has been linked to increased cell growth and metastasis. As Dr. Asano noted, "VIPR2 can form dimers, which alter its properties and enhance its oncogenic potential."

To investigate this, the research team conducted experiments on cell models and mouse models, demonstrating that VIPR2 can indeed homodimerize—two VIPR2 molecules binding together. This dimerization was found to facilitate tumor growth and metastasis through specific interactions at the receptor's transmembrane domains, which can either promote or inhibit dimerization based on the presence of certain peptides, specifically TM3-4 peptides.

According to co-corresponding author Dr. Yukio Ago, also a professor in the Department of Cellular and Molecular Pharmacology at Hiroshima University, the introduction of TM3-4 peptides effectively disrupted the dimerization of VIPR2. "This de-dimerization reduced the receptor's interaction with proteins that activate pathways associated with cell proliferation and metastasis," Dr. Ago explained. The results indicated that breast cancer cells expressing these peptides showed significantly suppressed tumor growth and reduced lymph-node metastasis.

The implications of these findings are profound, as they not only elucidate a critical mechanism underlying breast cancer progression but also pave the way for the development of targeted therapies. The researchers are now planning further studies to assess the anticancer effects of purified TM3-4 peptides in animal models, with the aim of creating innovative drugs that specifically target cancer cells exhibiting enhanced VIPR2 dimerization.

This research was supported by prestigious organizations including the Japan Society for the Promotion of Science and the Japan Agency for Medical Research and Development. The collaborative effort involved contributions from multiple departments within Hiroshima University, highlighting the interdisciplinary nature of this vital work.

Overall, the findings from Hiroshima University represent a promising advance in the field of cancer research, offering hope for more effective treatment options for patients battling breast cancer. As the researchers continue to explore the therapeutic potential of TM3-4 peptides, the scientific community watches closely, anticipating the next steps in the fight against this pervasive disease.