Researchers uncover how surrounding cells fuel triple-negative breast cancer growth

Triple-negative breast cancer, which accounts for approximately 10–15% of all breast cancer cases, is considered particularly difficult to treat because it grows rapidly and carries a high risk of recurrence.

Because targeted therapies used for other types of breast cancer have limited applicability to this subtype, treatment has relied largely on chemotherapy. However, drug resistance and recurrence have created an urgent need for new treatment and diagnostic approaches.

A research team led by Dr. Hyun-Soo Cho at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) in collaboration with Professor Keun Hur's team at Kyungpook National University, has identified how miR-1290, a type of microRNA transferred from fibroblasts surrounding tumors, promotes the growth of triple-negative breast cancer cells.

Fibroblasts normally provide structural support for tissues and help repair wounds. In the environment surrounding a tumor, however, they can instead support cancer growth. It remains unclear which substances these cells release to promote cancer cell growth.

The researchers focused on exosomes, tiny sacs released by cells that act like delivery packages, carrying various substances to other cells. By analyzing the contents of exosomes released by cancer-associated fibroblasts and breast cancer cells, the team identified miR-1290 as a key candidate involved in cancer growth.

When miR-1290 from fibroblasts entered triple-negative breast cancer cells, it reduced levels of TBC1D4, a protein that helps suppress tumor growth. This activated growth signals within the cancer cells, increased miR-1290 levels, and promoted cancer cell proliferation.

Based on this mechanism, the team proposed a new therapeutic approach that blocks the signals driving cancer cell growth. In experiments using three-dimensional cell models and animals, the researchers demonstrated that everolimus, a growth-inhibiting drug already approved for the treatment of other cancers, effectively suppressed cancer cell proliferation induced by miR-1290.

An analysis of blood miR-1290 levels in patients with breast cancer also showed that higher blood levels of miR-1290 were associated with faster cancer progression and poorer outcomes. These findings suggest that miR-1290 could serve as a blood-based biomarker for diagnosis and prognosis.

The study identifies a mechanism in the environment surrounding tumors that drives the growth of triple-negative breast cancer, a particularly challenging cancer to treat. It also opens up the possibility of repurposing an existing drug to target this mechanism.

This study reveals the signaling pathway through which cells surrounding a tumor stimulate cancer cells. We expect these findings to contribute to the development of new targeted therapies and more precise diagnostic criteria for patients with triple-negative breast cancer, whose treatment options remain limited."

Dr. Hyun-Soo Cho, study's lead investigator

The study was published online on September 20 in Signal Transduction and Targeted Therapy (Impact Factor: 81.2), a leading international journal in medicine and the life sciences.

The article is titled "Breast cancer-associated fibroblast-derived exosomal miR-1290 promotes triple-negative breast cancer cell proliferation." The corresponding authors are Drs. Hyun-Soo Cho, Tae-Su Han, Dae-Soo Kim, and Mi-Young Son of KRIBB, and the first authors are Dr. Jinkwon Lee and researcher Taesang Son, also of KRIBB.

This research was supported by the Bio and Medical Technology Development Program of the Ministry of Science and ICT, the Mid-Career Researcher Program of the National Research Foundation of Korea, and the Strategic Research Programs and Major Research Programs of the Korea Research Institute of Bioscience and Biotechnology (KRIBB).