Systemic Spread Is an Early Step in Breast Cancer

It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single...

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Bibliographic Details
Published in:	Cancer cell 2008-01, Vol.13 (1), p.58-68
Main Authors:	Hüsemann, Yves, Geigl, Jochen B., Schubert, Falk, Musiani, Piero, Meyer, Manfred, Burghart, Elke, Forni, Guido, Eils, Roland, Fehm, Tanja, Riethmüller, Gert, Klein, Christoph A.
Format:	Article
Language:	eng
Subjects:	Animals Bone Marrow Cells - pathology Breast Neoplasms - genetics Breast Neoplasms - pathology Cell Proliferation Cell Transformation, Neoplastic CELLCYCLE Epithelial Cells - pathology Female Gene Expression Regulation, Neoplastic Humans Karyotyping Lung Neoplasms - secondary Mammary Glands, Animal - transplantation Mammary Glands, Animal - ultrastructure Mammary Neoplasms, Experimental - genetics Mammary Neoplasms, Experimental - pathology Mice Mice, Inbred BALB C Mice, Transgenic Neoplasm Invasiveness Neoplasm Metastasis Neoplastic Cells, Circulating - pathology Precancerous Conditions - genetics Precancerous Conditions - pathology Siblings
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Summary:	It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single premalignant HER-2 transgenic glands displayed disseminated tumor cells and micrometastasis in bone marrow and lungs. The number of disseminated cancer cells and their karyotypic abnormalities were similar for small and large tumors in patients and mouse models. When activated by bone marrow transplantation into wild-type recipients, 80 early-disseminated cancer cells sufficed to induce lethal carcinosis. Therefore, release from dormancy of early-disseminated cancer cells may frequently account for metachronous metastasis.
ISSN:	1535-6108 1878-3686