The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Breast cancer is frequently diagnosed in women and poses a major health problem throughout the world. Currently, the unresponsiveness of cancer cells to chemotherapeutics is a major concern. During chemotherapeutic treatment with Doxorubicin, neighbouring cells in the tumor microenvironment are also damaged. Depending on the concentration of Doxorubicin, apoptotic or senescent fibroblasts in the tumor microenvironment can then secrete a variety of bioactive molecules which promote tumor growth, metastasis and drug resistance.
Mouse embryonic fibroblasts (MEFs) were treated with Doxorubicin to induce apoptosis and senescence respectively. Conditioned media was collected from the MEFs and was used to assess the paracrine effects between fibroblasts and E0771 murine breast cancer cells.
Senescent fibroblasts significantly increased cell viability in E0771 cells following Doxorubicin treatment by activating Akt and ERK. Autophagy contributed to cancer cell death and not to treatment resistance in breast cancer cells.
Our results highlight the complexity of the tumor microenvironment where chemotherapeutic agents such as Doxorubicin can induce significant changes fibroblasts which can affect tumor growth via the secretion of paracrine factors. Here we have demonstrated that those secreted paracrine factors enhance breast cancer growth and induce therapeutic resistance through the evasion of apoptotic cell death.
Description
CITATION: Carla, F., et al. 2019. The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells. Experimental Cell Research, 381(2):280-287. doi:10.1016/j.yexcr.2019.05.020
The original publication is available at https://www.sciencedirect.com/journal/experimental-cell-research
The Doctoral/Master’s degree for this article is available at [http://hdl.handle.net/10019.1/106181]
The original publication is available at https://www.sciencedirect.com/journal/experimental-cell-research
The Doctoral/Master’s degree for this article is available at [http://hdl.handle.net/10019.1/106181]
Keywords
Apoptosis -- Physiology, Breast -- Cancer -- Chemotherapy, Doxorubicin -- Chemotherapy, Fibroblasts, Senescence, Breast cancer -- Treatment resistance, Apoptosis -- Effect of drugs on, Drug resistance in cancer cells
Citation
Carla, F., et al. 2019. The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells. Experimental Cell Research, 381(2):280-287. doi:10.1016/j.yexcr.2019.05.020