Uncovering temperature-dependent extracellular vesicle secretion in breast cancer.

In all living things, temperature is a key factor to maintain function and survive. Animals and plants need to adapt temperature change with optimizing their behaviour and growth by sensing temperature. Similarly, tumour cells must adapt continuously to fluctuations in external conditions including temperature. To find a better environment, cancer cells promote growth and metastasis, which contributes to tumour malignancy. Pathological studies in breast cancer have implied that temperature is associated with disease progression. However, no clear mechanisms have emerged for how thermal changes affect tumour cells and their gene regulation in tumour development and malignancy. Here we discovered the temperature-dependent extracellular vesicle (EV) secretion in breast cancer. Cancer cell growth and EV secretion increased in a temperature-dependent manner, which indicated that temperatures were associated with poor prognosis in breast cancer patients. We also found that low-density lipoprotein receptor (LDLR), a responsible gene for temperature-dependent EV secretion, was upregulated with the increase in temperature. Consistent with our results, LDLR gene has been characterized and identified as a key factor for malignancy in a wide range of cancers. Our findings shed new light on tumour aggressiveness and therapeutic strategies for breast cancer, especially regarding EV formation and secretion, thus providing a new relationship between cancer and EV biology in the light of temperature.