TY - JOUR
T1 - BCRP drives intrinsic chemoresistance in chemotherapy-naïve breast cancer brain metastasis
AU - Uceda-Castro, Rebeca
AU - Margarido, Andreia S.
AU - Song, Ji-Ying
AU - de Gooijer, Mark C.
AU - Messal, Hendrik A.
AU - Chambers, Cecilia R.
AU - Nobis, Max
AU - Çitirikkaya, Ceren H.
AU - Hahn, Kerstin
AU - Seinstra, Danielle
AU - Herrmann, David
AU - Timpson, Paul
AU - Wesseling, Pieter
AU - van Tellingen, Olaf
AU - Vennin, Claire
AU - van Rheenen, Jacco
N1 - Publisher Copyright: © 2023 The Authors.
PY - 2023/10/20
Y1 - 2023/10/20
N2 - Although initially successful, treatments with chemotherapy often fail because of the recurrence of chemoresistant metastases. Since these tumors develop after treatment, resistance is generally thought to occur in response to chemotherapy. However, alternative mechanisms of intrinsic chemoresistance in the chemotherapynaïve setting may exist but remain poorly understood. Here, we study drug-naïve murine breast cancer brain metastases (BCBMs) to identify how cancer cells growing in a secondary site can acquire intrinsic chemoresistance without cytotoxic agent exposure. We demonstrate that drug-naïve murine breast cancer cells that form cancer lesions in the brain undergo vascular mimicry and concomitantly express the adenosine 50-triphosphate- binding cassette transporter breast cancer resistance protein (BCRP), a common marker of brain endothelial cells. We reveal that expression of BCRP by the BCBM tumor cells protects them against doxorubicin and topotecan. We conclude that BCRP overexpression can cause intrinsic chemoresistance in cancer cells growing in metastatic sites without prior chemotherapy exposure.
AB - Although initially successful, treatments with chemotherapy often fail because of the recurrence of chemoresistant metastases. Since these tumors develop after treatment, resistance is generally thought to occur in response to chemotherapy. However, alternative mechanisms of intrinsic chemoresistance in the chemotherapynaïve setting may exist but remain poorly understood. Here, we study drug-naïve murine breast cancer brain metastases (BCBMs) to identify how cancer cells growing in a secondary site can acquire intrinsic chemoresistance without cytotoxic agent exposure. We demonstrate that drug-naïve murine breast cancer cells that form cancer lesions in the brain undergo vascular mimicry and concomitantly express the adenosine 50-triphosphate- binding cassette transporter breast cancer resistance protein (BCRP), a common marker of brain endothelial cells. We reveal that expression of BCRP by the BCBM tumor cells protects them against doxorubicin and topotecan. We conclude that BCRP overexpression can cause intrinsic chemoresistance in cancer cells growing in metastatic sites without prior chemotherapy exposure.
UR - http://www.scopus.com/inward/record.url?scp=85174750491&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/sciadv.abp9530
DO - https://doi.org/10.1126/sciadv.abp9530
M3 - Article
C2 - 37851804
SN - 2375-2548
VL - 9
SP - eabp9530
JO - Science advances
JF - Science advances
IS - 42
M1 - abp9530
ER -