Abstract
The establishment of clinically relevant models for tumor metastasis and drug testing is a major challenge in cancer research. Here we report a physiologically relevant assay enabling quantitative analysis of metastatic capacity of tumor cells following implantation into the chorioallantoic membrane (CAM). Engraftment of as few as 103 non-small cell lung cancer (NSCLC) and prostate cancer (PCa) cell lines was sufficient for both primary tumor and metastasis formation. Standard 2D-imaging as well as 3D optical tomography imaging were used for the detection of fluorescent metastatic foci in the chick embryo. H2228- and H1975-initiated metastases were confirmed by genomic analysis. We quantified the inhibitory effect of docetaxel on LNCaP, and that of cisplatin on A549- and H1299-initiated metastatic growths.The CAM assay also mimicked the sensitivity of ALK-rearranged H2228 and EGFR-mutated H1975 NSCLC cells to tyrosine kinase inhibitors crizotinib and gefitinib respectively, as well as sensitivity of LNCaP cells to androgen-dependent enzalutamide therapy. The assay was suggested to reconstitute the bone metastatic tropism of PCa cells. We show that the CAM chick embryo model may be a powerful preclinical platform for testing and targeting of the metastatic capacity of cancer cells.
Highlights
The establishment of clinically relevant models for tumor metastasis and drug testing is a major challenge in cancer research
We adapted a similar protocol to a panel of non-small cell lung cancer (NSCLC) and prostate cancer (PCa) cell lines (Supplementary Table 1)
Reproducible results were obtained by implantation of 1 03 cells per egg, resulting in up to 80% of successfully formed nodules in the case of lung cancer cell lines (Fig. 1B) and 100% for prostate cancer cell lines
Summary
The establishment of clinically relevant models for tumor metastasis and drug testing is a major challenge in cancer research. We report a physiologically relevant assay enabling quantitative analysis of metastatic capacity of tumor cells following implantation into the chorioallantoic membrane (CAM). We show that the CAM chick embryo model may be a powerful preclinical platform for testing and targeting of the metastatic capacity of cancer cells. Diverse sites of tumor engraftment were applied, such as orthotopically or directly in the vascular system Both rarely reflect the real patient metastatic. To overcome some of these limitations and to bridge the gap between in vitro and in vivo study of metastasis, we and others attempted to use a chorioallantoic membrane (CAM) chick embryo model. U981 “Identification of Molecular Predictors and New Targets for Cancer Treatment”, INSERM, 94805 Villejuif, France. 2“Circulating Tumor Cells” Translational Platform, UMS AMMICa CNRS 3655‐INSERM US23, Gustave
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