3D model to study drug resistance of breast cancer cells
2017
Universidad de Buenos Aires, Buenos Aires, Argentina
Breast cancer stem cells that express HER2 can develop resistance to Trastuzumab. Recently, it was shown that breast cancer cells cultures as spheroids in a 3D environment developed autophagy and apoptosis, which induced drug resistance in HER2 overexpressing cells. Here, human mammary adenocarcinoma cells were cultured in 3D under hypoxic conditions. The results showed that culturing breast cancer cells in adverse conditions modulated the response to Trastuzumab. Moreover, in HER2+ cells, there was an increase in the breast cancer stem cell population. The 3D environment determined the expression of HER2 in breast cancer spheroids, where treatment with Trastuzumab induced the acquisition of resistance and the increase of the number of cancer stem cells, which had higher HER2 expression. Contrary, cells with low HER2 expression showed more sensitivity to Trastuzumab and decreased the number of cancer stem cells. Overall, the researchers show a link between 3D structures and the modulation of breast cancer stem cell population and HER2 expression which, in turn, regulates the response to Trastuzumab.
Breast cancer stem cells are involved in Trastuzumab resistance through the HER2 modulation in 3D culture
Gabriel L Fiszman
Added on: 10-08-2021
[1] https://onlinelibrary.wiley.com/doi/10.1002/jcb.26298[2] https://data.jrc.ec.europa.eu/dataset/ffebe454-ed9a-47cf-8a33-8cf70c1b7d38