New potential target for breast cancer treatment
Researchers at OnkPat have found that breast cancer stem cells are dependent on a certain estrogen receptor to survive. The findings, which are presented in Journal of the National Cancer Institute opens up for new treatment strategies for breast cancer.
Most forms of breast cancer are dependent on estrogen for their growth and the expression of estrogen receptors in the tumor is often used to decide the treatment strategy. There are two different forms of estrogen receptors, alpha and beta, where alpha is the one most commonly found in normal breast cancer cells.
A specific type of breast cancer cell is the breast cancer stem cell. These cells can be found in all types of breast cancer, but are more abundant in the more aggressive forms of breast cancer. These cells have stem cell properties and a high proliferative and metastatic potential. They are also often resistant to conventional treatment and many researchers believe that the cancer stem cells need to be eradicated in order to cure metastatic disease.
-It has previously been believed that breast cancer stem cells are lacking estrogen receptors and that they are affected by estrogen via adjacent cells. We have now found that they actually express estrogen receptor beta, and that they are dependent on estrogen for cell division and survival, says principal investigator Johan Hartman, associate professor at the Department of Oncology-Pathology.
Extensive characterization of cancer stem cells
The researchers have extensively studied cancer stem cells originating from a large number of breast cancer patients. To grow the cancer stem cells, the researchers have cultured the isolated cells as mammospheres. In this method to enrich for the cancer stem cells, the cells are grown floating in the culture medium instead of at the surface of the culture dish as in a conventional cell culture. It was shown that the division of these cells could be inhibited by selectively blocking the estrogen receptor beta.
The study also consisted of experiments in mice with xenografts of human breast cancer tumors. It was shown that the tumor growth was stopped when combining conventional treatment with blocking of estrogen receptor beta.
-We hope our research will lead to improvement of breast cancer treatment and that also the breast cancer stem cells can be targeted, says Johan Hartman.
The study was financed with grants from several bodies, including the Swedish Society for Medical Research (SSMF), the Swedish Cancer Society and Stockholm County Council.
Estrogen receptor β as a therapeutic target in breast cancer stem cells
Ran Ma, Govindasamy-Muralidharan Karthik, John Lövrot, Felix Haglund, Gustaf Rosin, Anne Katchy, Xiaonan Zhang, Lisa Viberg, Jan Frisell, Cecilia Williams, Stig Linder, Irma Fredriksson, Johan Hartman
Journal of the National Cancer Institute, online 10 February 2017, doi:10.1093/jnci/djw236