Tumor Extrinsic Factors Mediate Primary T-DM1 Resistance in HER2-Positive Breast Cancer Cells.

ABSTRACT: To explore if the tumor microenvironment contributes to the primary resistance of HER2-positive breast cancer cells to T-DM1, we examined whether Matrigel, a basement membrane matrix that provides a three-dimensional (3D) cell culture condition, caused the primary resistance of HER2-positive, T-DM1-sensitive breast cancer cells (JIMT1 and SKBR-3 cells) to T-DM1. This is different from the conventional approach such that the cells are exposed with escalated doses of drug to establish a drug-resistant cell line. We found that these cells were able to grow and form spheroids on the Matrigel in the presence of T-DM1. We further explored the molecular mechanisms that enables these cells to be primarily resistant to T-DM1 and found that EGFR was activated in the spheroids, leading to an increase

SUBMITTER: Endo Y 

PROVIDER: S-EPMC8150545 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature