Rapid extravasation and establishment of breast cancer micrometastases in the liver microenvironment

Michelle D. Martin, Gert Jan Kremers, Kurt W. Short, Jonathan V. Rocheleau, Lei Xu, David W. Piston, Lynn M. Matrisian, D. Lee Gorden

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


To examine the interplay between tumor cells and the microenvironment during early breast cancer metastasis, we developed a technique for ex vivo imaging of murine tissue explants using two-photon microscopy. Cancer cells in the liver and the lung were compared by imaging both organs at specific time points after the injection of the same polyomavirus middle T-initiated murine mammary tumor cell line. Extravasation was greatly reduced in the lung compared with the liver, with 56% of tumor cells in the liver having extravasated by 24 hours, compared with only 22% of tumor cells in the lung that have extravasated. In the liver, imaged cells continually transitioned from an intravascular location to an extravascular site, whereas in the lung, extravasation rates slowed after 6 hours. Within the liver microenvironment, the average size of the imaged micrometastatic lesions increased 4-fold between days 5 and 12. Histologic analysis of these lesions determined that by day 12, the micrometastases were heterogeneous, consisting of both tumor cells and von Willebrand factor-positive endothelial cells. Further analysis with intravenously administered lectin indicated that vessels within the micrometastatic tumor foci were patent by day 12. These data present the use of two-photon microscopy to directly compare extravasation times in metastatic sites using the same tumor cell line and highlight the differences in early events and metastatic patterns between two important secondary sites of breast cancer progression with implications for future therapy.

Original languageEnglish
Pages (from-to)1319-1327
Number of pages9
JournalMolecular Cancer Research
Issue number10
StatePublished - Oct 2010


Dive into the research topics of 'Rapid extravasation and establishment of breast cancer micrometastases in the liver microenvironment'. Together they form a unique fingerprint.

Cite this