Imaging amoeboid cancer cell motility in vivo

Abstract

Summary The availability of multi‐photon intravital microscopy has recently allowed researchers to start to visualise the dynamic behaviour of cancer cells in vivo. This imaging has revealed that many cancer cells ranging from carcinoma to melanoma move in an amoeboid manner in order to invade surrounding tissue and escape from the primary tumour. This mode on cell motility is extremely rapid and does not require the activity of proteases to degrade the extra‐cellular matrix (ECM). This review details the techniques that are available to study cell motility in vivo and discusses the current knowledge about the mechanisms of amoeboid cell motility.

Visualizing extravasation dynamics of metastatic tumor cells

“…The integrin-independent mode of extravasation used by MDAtwist cells might be facilitated by strong membrane-protrusive forces that directly penetrate the endothelium without the need for substrate adhesion. A highly protrusive cell phenotype similar to that displayed by MDAtwist cells has been associated with an amoeboid-like mode of tumor cell migration, which can be independent of integrin adhesions and ECM degradation (Friedl, 2004;Pinner and Sahai, 2008;Wolf et al, 2003). Interestingly, Twist has been shown to regulate the small GTPase RhoC, which in turn regulates ROCK, myosin contractility and formation of rounded protrusions (Ma et al, 2007;Narumiya et al, 2009).…”

“…In MDAwt cells, 1 integrins mediate extravasation through an alternative mechanism, because Y27632 did not prevent this process. In this case, movement and extravasation of tumor cells might be mediated more through integrin-adhesion mechanisms that induce actin polymerization leading to invadapodia formation and/or cell locomotion and vascularremodeling events (Friedl, 2004;Pinner and Sahai, 2008;Wolf et al, 2003). Interestingly, VEGFA-mediated tumor cell extravasation also relies on expression of 1 integrin and is associated with vascular remodeling.…”

α2-Macroglobulin Inhibits the Malignant Properties of Astrocytoma Cells by Impeding β-Catenin Signaling

“…Tumor cells invade extracellular matrix either through protease-dependent processes or amoeboid movement (24). Therefore, inhibiting extracellular proteases would eventually reduce the ability of cells to invade the matrix network.…”

Intravital microscopy: new insights into metastasis of tumors

“…Both in vitro and in vivo experiments have shown that mysenchymal migration is characterized by secretion of proteases and an elongated polarized cell morphology, whereas amoeboid movement is characterized by a non-polarized flexible round morphology of the cell and does not require any proteolytic activity (Wolf et al, 2003;Wolf et al, 2007;Wyckoff et al, 2007;Sahai and Marshall, 2003). The amoeboid mode of migration enables cells to squeeze through small gaps by forming bleb-like structures, thereby pushing these fibers out of the way without the requirement for proteolytic activity (Pinner and Sahai, 2008), allowing them to migrate within mammary tumors with high velocity (Wyckoff et al, 2006;Wyckoff et al, 2007). Although amoeboid movement does not depend on ECM layer breakdown, it might be facilitated by other peptidase-dependent processes, such as the activation of chemokines.…”

“…For example, Pinner and colleagues engineered melanoma tumor cells to express GFP driven by the Brn-2 promoter, and showed that melanoma cells can switch from a less differentiated state to a differentiated state when these cells exit the primary tumor and enter the secondary site (Pinner and Sahai, 2008). These types of IVM experiments will be able to answer long-standing questions in the field, such as whether cells can transiently switch from an epithelial to a mesenchymal phenotype (EMT) during metastasis, or whether the metastasizing tumor cells have a stem cell phenotype.…”