Intravital Microscopy Through an Abdominal Imaging Window Reveals a Pre-Micrometastasis Stage During Liver Metastasis
- 31 October 2012
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 4 (158), 158ra145
- https://doi.org/10.1126/scitranslmed.3004394
Abstract
Cell dynamics in subcutaneous and breast tumors can be studied through conventional imaging windows with intravital microscopy. By contrast, visualization of the formation of metastasis has been hampered by the lack of long-term imaging windows for metastasis-prone organs, such as the liver. We developed an abdominal imaging window (AIW) to visualize distinct biological processes in the spleen, kidney, small intestine, pancreas, and liver. The AIW can be used to visualize processes for up to 1 month, as we demonstrate with islet cell transplantation. Furthermore, we have used the AIW to image the single steps of metastasis formation in the liver over the course of 14 days. We observed that single extravasated tumor cells proliferated to form “pre-micrometastases,” in which cells lacked contact with neighboring tumor cells and were active and motile within the confined region of the growing clone. The clones then condensed into micrometastases where cell migration was strongly diminished but proliferation continued. Moreover, the metastatic load was reduced by suppressing tumor cell migration in the pre-micrometastases. We suggest that tumor cell migration within pre-micrometastases is a contributing step that can be targeted therapeutically during liver metastasis formation.Keywords
This publication has 40 references indexed in Scilit:
- P-Cadherin Promotes Liver Metastasis and Is Associated with Poor Prognosis in Colon CancerThe American Journal of Pathology, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Circulating Tumor Cells as a Window on Metastasis Biology in Lung CancerThe American Journal of Pathology, 2011
- Stabilized imaging of immune surveillance in the mouse lungNature Methods, 2010
- Intravital microscopy as a tool to study drug delivery in preclinical studiesAdvanced Drug Delivery Reviews, 2010
- In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammationProceedings of the National Academy of Sciences, 2010
- Intravital imaging of stromal cell dynamics in tumorsCurrent Opinion in Genetics & Development, 2009
- In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblastsNature Methods, 2009
- Intravital imaging of metastatic behavior through a mammary imaging windowNature Methods, 2008
- Illuminating the metastatic processNature Reviews Cancer, 2007