The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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doi: 10.1158/0008-5472.CAN-24-2022.
Summary of the findings
Summary of the findingsBreast cancer (BC), the most prevalent cancer in women, is marked by heterogeneity in its presentation. Despite the availability of published cell lines, most studies revert to a limited amount of models, and more than half of them rely on MCF-7 cells, failing to recapitulate disease heterogeneity. This study presents the largest and most comprehensively characterized collection of orthotopic BC cell line-derived xenograft (CDX) models to date. Using both mammary intraductal (MIND) and fat-pad transplantation (FPT) approaches, the authors established CDX models from 20 human BC cell lines representing all major molecular subtypes. These models faithfully recapitulate the full spectrum of BC progression, from in situ lesions to metastatic disease. Pathological evaluation revealed two distinct tumor morphologies, flat and nodular, which were largely determined by the mode of transplantation and intrinsic properties of the cell lines. Transcriptomic profiling implicated the TGF-β signaling pathway as a key regulator of this morphological divergence. Functional validation showed that SMAD4 knockout suppressed nodular growth, while constitutive activation of TGFBR1 enhanced tumor aggressiveness. Overall, this work identifies TGF-β signaling as a central driver of BC morphology and progression, and provides a robust and versatile resource of CDX models to support mechanistic and translational BC research.
Future impact
