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Open AccessArticle

The Detection and Morphological Analysis of Circulating Tumor and Host Cells in Breast Cancer Xenograft Models

Biomarkers Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Authors to whom correspondence should be addressed.
These authors share senior authorship.
Cells 2019, 8(7), 683;
Received: 4 June 2019 / Revised: 1 July 2019 / Accepted: 1 July 2019 / Published: 5 July 2019
Hematogenous dissemination may occur early in breast cancer (BC). Experimental models could clarify mechanisms, but in their development, the heterogeneity of this neoplasia must be considered. Here, we describe circulating tumor cells (CTCs) and the metastatic behavior of several BC cell lines in xenografts. MDA-MB-231, BT-474, MDA-MB-453 and MDA-MB-468 cells were injected at the orthotopic level in immunocompromised mice. CTCs were isolated using a size-based method and identified by cytomorphological criteria. Metastases were detected by COX IV immunohistochemistry. CTCs were detected in 90% of animals in each model. In MDA-MB-231, CTCs were observed after 5 weeks from the injection and step wisely increased at later time points. In animals injected with less aggressive cell lines, the load of single CTCs (mean ± SD CTCs/mL: 1.8 ± 1.3 in BT-474, 122.2 ± 278.5 in MDA-MB-453, 3.4 ± 2.5 in MDA-MB-468) and the frequency of CTC clusters (overall 38%) were lower compared to MDA-MB-231 (946.9 ± 2882.1; 73%). All models had lung metastases, MDA-MB-453 and MDA-MB-468 had ovarian foci too, whereas lymph nodal involvement was observed in MDA-MB-231 and MDA-MB-468 only. Interestingly, CTCs showed morphological heterogeneity and were rarely associated to host cells. Orthotopic xenograft of BC cell lines offers valid models of hematogenous dissemination and a possible experimental setting to study CTC-blood microenvironment interactions. View Full-Text
Keywords: circulating tumor cells; metastasis; xenograft models; breast cancer circulating tumor cells; metastasis; xenograft models; breast cancer
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Cleris, L.; Daidone, M.G.; Fina, E.; Cappelletti, V. The Detection and Morphological Analysis of Circulating Tumor and Host Cells in Breast Cancer Xenograft Models. Cells 2019, 8, 683.

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