Imaging of liver premicrometastases identified a link between cell migration and outgrowth.

  • Major finding: Imaging of liver premicrometastases identified a link between cell migration and outgrowth.

  • Approach: High-resolution imaging through an abdominal window was used for long-term study of metastasis.

  • Impact: This technique can also be used to dissect biologic processes in other abdominal organs.

Intravital microscopy using imaging windows in tumor-bearing mice has provided insight into the complex, multistep process of metastasis. However, existing windows are not well suited for long-term visualization of metastasis-prone abdominal organs, such as the lung and liver. To better study the dynamics of metastatic colonization, Ritsma and colleagues developed an abdominal imaging window (AIW) consisting of a titanium ring and a coverslip inserted into the skin and abdominal wall of mice using purse-string sutures. The AIW remained securely in place, did not impair the mobility or health of the animals, and did not alter abdominal tissue structure. Long-term imaging through the AIW enabled visualization of biologic processes in various abdominal organs, including stem cell division in the small intestine, islet cell engraftment in the kidney, and immune responses in the spleen, suggesting that this technique may have broad applications. Furthermore, the AIW allowed for imaging of clonal metastatic outgrowth from single fluorescently labeled colorectal tumor cells in a standardized liver metastasis assay. Tracking of proliferating tumor cells at subcellular resolution suggested that tumor cells grow into loosely packed premicrometastases in which cells are migratory and subsequently condense into micrometastases in which cells are nonmotile. Indeed, quantification of cell motility revealed enhanced migration of these premicrometastatic cells compared with cells within micrometastases, which did not form protrusions. Suppression of colorectal tumor cell migration using a phospholipase C inhibitor or LIM kinase overexpression specifically diminished the proliferation of premicrometastatic cells but not cells at later stages and resulted in decreased formation of larger metastatic outgrowths. Although further research is necessary to confirm these data in other tumor models and in human samples, these findings suggest a contribution for migration in the early steps of colonization and that blockade of this process may limit metastatic outgrowth.

Ritsma L, Steller EJ, Beerling E, Loomans CJ, Zomer A, Gerlach C, et al. Intravital microscopy through an abdominal imaging window reveals a pre-micrometastasis stage during liver metastasis. Sci Transl Med 2012;4:158ra145.

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