bims-netuvo 2025-06-29 papers

Nature. 2025 Jun 25.

Nerve-to-cancer transfer of mitochondria during cancer metastasis.

Gregory Hoover, Shila Gilbert, Olivia Curley, Clémence Obellianne, Mike T Lin, William Hixson, Terry W Pierce, Joel F Andrews, Mikhail F Alexeyev, Yi Ding, Ping Bu, Fariba Behbod, Daniel Medina, Jeffrey T Chang, Gustavo Ayala, Simon Grelet.

The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve-cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve-cancer coculture models confirmed that neurons significantly improve tumour energetics. Neurons cocultured with cancer cells undergo metabolic reprogramming, resulting in increased mitochondrial mass and subsequent transfer of mitochondria to adjacent cancer cells. To precisely track the fate of recipient cells, we developed MitoTRACER, a reporter of cell-to-cell mitochondrial transfer that permanently labels recipient cancer cells and their progeny. Lineage tracing and fate mapping of cancer cells acquiring neuronal mitochondria in primary tumours revealed their selective enrichment at metastatic sites following dissemination. Collectively, our data highlight the enhanced metastatic capabilities of cancer cells that receive mitochondria from neurons in primary tumours, shedding new light on how the nervous system supports cancer metabolism and metastatic dissemination.

DOI: https://doi.org/10.1038/s41586-025-09176-8

Science. 2025 Jun 26. 388(6754): 1357-1358

Tumors may get energy boost from nerve cells' mitochondria.

Mitch Leslie.

Study shows the organelles traveling through "bridges" into nearby cancer cells.

DOI: https://doi.org/10.1126/science.aea0605

Front Pharmacol. 2025 ;16 1540027

The supporting role of Schwann cells in perineural invasion of pancreatic ductal adenocarcinoma.

Yun He, Zheng Chen, Liu Yang, Shuanying Qiao, Zonghua Su, Feng Ding, Fadian Ding, Fuli Xin, Siyu Xiang, Aiping Lyu, Fangfei Li.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer, with tumor cells readily disseminating to other organs through the bloodstream, lymphatic system, and nervous system, thereby impacting patients' survival rates. PDAC is often associated with perineural invasion (PNI), which not only facilitates tumor spread but may also lead to symptoms such as pain, further affecting the patient's quality of life. PNI is frequently observed in PDAC and has become an important histopathological marker associated with poor clinical outcomes. Many studies suggest that a high density of Schwann cells (SCs) is typically found in areas of PNI in PDAC. What's more, as the primary glial cells in the PNS, SCs actively contribute to pancreatic tumour progression by releasing substances capable of interacting with cancer cells and promoting cancer cells proliferation and migration in tumor microenvironment (TME). Therefore, SCs are crucial in the interactions between nerves and tumors as the primary glial cells within PNS. In this review, our objective is to present novel insights and perspectives for PDAC therapy that targets SCs and related signal pathways to decrease PNI, thereby reduce pain and prolong survival in cancer patients. We detail and summarize the multiple mechanisms by which SCs promote PNI in tumors and thus lead to malignancy.

Keywords: Schwann cells; pancreatic ductal adenocarcinoma; perineural invasion; peripheral nervous system; tumor microenvironment

DOI: https://doi.org/10.3389/fphar.2025.1540027