Cancer cell motility: lessons from migration in confined spaces

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Abstract

This Opinion article discusses the various migration modes used by cancer cells in confining microenvironments and explains how understanding confined cancer cell motility in vivo through the application of engineered in vitro models could help to develop therapeutic approaches to prevent metastases.

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Real-time imaging reveals the single steps of brain metastasis formation.

Yvonne Kienast, Louisa von Baumgarten, Martin Fuhrmann … (2010)

Brain metastasis frequently occurs in individuals with cancer and is often fatal. We used multiphoton laser scanning microscopy to image the single steps of metastasis formation in real time. Thus, it was possible to track the fate of individual metastasizing cancer cells in vivo in relation to blood vessels deep in the mouse brain over minutes to months. The essential steps in this model were arrest at vascular branch points, early extravasation, persistent close contacts to microvessels and perivascular growth by vessel cooption (melanoma) or early angiogenesis (lung cancer). Inefficient steps differed between the tumor types. Long-term dormancy was only observed for single perivascular cancer cells, some of which moved continuously. Vascular endothelial growth factor-A (VEGF-A) inhibition induced long-term dormancy of lung cancer micrometastases by preventing angiogenic growth to macrometastases. The ability to image the establishment of brain metastases in vivo provides new insights into their evolution and response to therapies.

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AACR centennial series: the biology of cancer metastasis: historical perspective.

James E. Talmadge, Isaiah Fidler (2010)

Metastasis resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His "seed and soil" hypothesis was substantiated a century later with experimental studies, and numerous reports have confirmed these seminal observations. An improved understanding of the metastatic process and the attributes of the cells selected by this process is critical for the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, so metastasis prevention may not be relevant. Treating systemic disease and identifying patients with early disease should be our goal. Revitalized research in the past three decades has focused on new discoveries in the biology of metastasis. Even though our understanding of molecular events that regulate metastasis has improved, the contributions and timing of molecular lesion(s) involved in metastasis pathogenesis remain unclear. Review of the history of pioneering observations and discussion of current controversies should increase understanding of the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and should lead to the design of successful therapy. (c)2010 AACR.

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Random versus directionally persistent cell migration.

Ryan Petrie, Andrew Doyle, Kenneth M. Yamada (2009)

Directional migration is an important component of cell motility. Although the basic mechanisms of random cell movement are well characterized, no single model explains the complex regulation of directional migration. Multiple factors operate at each step of cell migration to stabilize lamellipodia and maintain directional migration. Factors such as the topography of the extracellular matrix, the cellular polarity machinery, receptor signalling, integrin trafficking, integrin co-receptors and actomyosin contraction converge on regulation of the Rho family of GTPases and the control of lamellipodial protrusions to promote directional migration.