Neither epithelial nor mesenchymal circulating tumor cells isolated from breast cancer patients are tumorigenic in NOD- scid Il2rg null mice

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The quantitative evaluation of circulating EpCAM+ tumor cells (CTCs) in the peripheral blood of breast cancer patients provides an independent predictor of risk of progression in patients with metastatic disease. The present study investigated the tumorigenic potential of CTCs from cryopreserved mobilized leukapheresis products obtained from three metastatic breast cancer patients in remission. Cells were immunomagnetically separated if they expressed either the epithelial cell surface marker EpCAM, or CD90, a mesenchymal stromal cell marker associated with tumorigenic stem-like cancer cells. Cells were injected into the mammary fat pads of NOD-scid Il2rg null mice. The injection of very large numbers of CTCs (0.3-1.5×10 6 CTCs per site, 20 sites per sample) in an optimized xenograft model did not result in the establishment of human-derived tumor xenografts. Four orders of magnitude fewer cells of the same CD90+ phenotype, but obtained from metastatic breast cancer pleural effusions, were highly tumorigenic in the same model system. These results favor the interpretation that circulating tumor cell load does not directly bear on metastatic potential, and that tumorigenic circulating breast cancer cells in patients with metastatic breast cancer are exceedingly rare. Furthermore, the CD44+/CD90+ phenotypic signature indicative of tumorigenicity in cells separated from metastatic

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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