Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

In this study, we examined the hypothesis that early pulmonary metastases form within the vasculature. We introduced primary tumors in immunocompromised mice by subcutaneous injection of murine breast carcinoma cells (4T1) expressing green fluorescent protein. Isolated ventilated and perfused lungs from these mice were examined at various times after tumor formation by fluorescent microscopy. The vasculature was visualized by counterstaining with 1,1-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI)-acetylated low-density lipoprotein. These experiments showed that metastatic cells derived by spontaneous metastases were intravascular, and that early colony formation was intravascular. The location of the tumor cells was confirmed by deconvolution analysis. This work extends our previous study(1) that sarcoma cells injected intravenously form intravascular colonies to spontaneous metastasis and to a carcinoma model system. Many of the tumor cells seen were single implying that tumor cells may travel as single cells. These results support a model for pulmonary metastasis in mice in which 1) tumor cells can attach to lung endothelium soon after arrival; 2) surviving tumor cells proliferate intravascularly in this model; and 3) extravasation of the tumor occurs when intravascular micrometastatic foci outgrow the vessels they are in.

Original publication




Journal article


Am J Pathol

Publication Date





749 - 753


Animals, Blood Vessels, Female, Green Fluorescent Proteins, Luminescent Proteins, Lung, Lung Neoplasms, Mice, Neoplasm Metastasis, Neoplasm Transplantation