Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

TLDR

The study aims to investigate breast cancer stem cells’ role in metastasis by creating patient‑derived orthotopic mouse models and employing noninvasive imaging to dissect dissemination mechanisms and evaluate therapeutic strategies. The authors generated patient‑derived orthotopic mouse models labeled with optical reporter fusion genes and used noninvasive imaging to track as few as ten labeled BCSCs in vivo, enabling study of early tumor growth and spontaneous metastasis. The models faithfully reproduce spontaneous metastasis and show that CD44⁺ cells from primary tumors and lung metastases are highly enriched for tumor‑initiating capacity.

Abstract

To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44(+) cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy.