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Drug sensitivity depends on cancer cell-extracellular matrix interactions

2018
Griffith University, Brisbane, Australia
One of the main limitations in cancer therapy is drug resistance from cancer cells. This can be due to de novo mechanisms acquired by the cells during normal cancer progression. However, traditional 2D models have limitations in faithfully replicating cell behaviour in vitro. Here, a 3D model based on Matrigel-embedded human breast cancer cells is used to investigate the response of cancer cells to doxorubicin and the potential acquisition of drug resistance. The results showed that the response of cancer cells grown in 3D conditions to doxorubicin are different compared to those in traditional models. Despite the reduced proliferation of cancer cells in 3D conditions, an increase in pro-survival proteins was observed following exposure to doxorubicin. Furthermore, interactions between the extracellular matrix and cancer cells were identified to be critical for the development of drug resistance. Accordingly, combining the inhibition of integrins signalling with doxorubicin could counteract the effect of this interplay and reduce breast cancer cell viability. Overall, the researchers present a new model that allows to study complex interactions of cancer cells with their environment and elucidate potential mechanisms that contribute to drug sensitivity.
Doxorubicin resistance in breast cancer cells is mediated by extracellular matrix proteins
Vicky M Avery
#1035
Added on: 10-20-2021
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