Profiling distinct mechanisms of tumour invasion for drug discovery: imaging adhesion, signalling and matrix turnover

Carragher, Neil O.

doi:10.1007/s10585-008-9222-y

Cited by 30 publications

(28 citation statements)

References 111 publications

(155 reference statements)

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“…Plasticity between distinct tumor invasion mechanisms enables rapid adaption of tumor invasion in response to environmental factors including pharmacological intervention. Such mechanistic adaptation may explain conflicting pharmacological responses observed between distinct tumor cell models and recorded clinical resistance to potential anti-invasive therapies such as MMP inhibitors [19]. Further studies using live cell confocal microscopy uncover the influence that stromal cell types, within the tumor microenvironment, have upon tumor invasion [20].…”

Section: Live-cell Imaging In Vitro: Technical Advances and Novel Appmentioning

confidence: 99%

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

et al. 2011

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Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates.

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Section: Live-cell Imaging In Vitro: Technical Advances and Novel Appmentioning

confidence: 99%

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

et al. 2011

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“…It provides cellular and temporal resolution which is already enough to characterise the type of 3D invasion which can be depicted as either single (mesnchymal or amoeboid) or collective migration [1, 109, 110, 116]. Confocal microscopy is the most suitable imaging technique to collect fixed endpoints or time-lapse sequences of three-dimensional data of migrating cells and matrix adhesion activities [117–120]. Advanced bioinformatics is needed to further process the data and apply multiparametric image analysis to describe cell behaviour with several parameters [117, 121, 122].…”

Section: Optical Imaging Towards Understanding Tumour Cell Migration mentioning

confidence: 99%

“…Confocal microscopy is the most suitable imaging technique to collect fixed endpoints or time-lapse sequences of three-dimensional data of migrating cells and matrix adhesion activities [117–120]. Advanced bioinformatics is needed to further process the data and apply multiparametric image analysis to describe cell behaviour with several parameters [117, 121, 122]. In Table 3, we recapitulate the challenges and potential solutions to make the 3D culture system a versatile model for understanding tumour invasion mechanisms.…”

Section: Optical Imaging Towards Understanding Tumour Cell Migration mentioning

confidence: 99%

Systems microscopy approaches to understand cancer cell migration and metastasis

Dévédec

Yan

Bont

et al. 2010

Cell. Mol. Life Sci.

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Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration.

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“…Recently, tumour therapeutic targets have expanded into the non-cytotoxic domain with the objective of curbing cancer metastasis [3], in addition to the traditional chemotherapy and radiotherapy approaches. To screen for such non-cytotoxic drugs that can specifically inhibit pathological cell movement, it is necessary to develop a functional assay that can quantify the extent of cell migration and invasion through the tissue environment under the influence of these drugs [4,5].…”

Section: Introductionmentioning

confidence: 99%

Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

Sun

Lim

Kurniawan

2014

J. R. Soc. Interface.

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Cancer metastasis involves the dissemination of cancer cells from the primary tumour site and is responsible for the majority of solid tumour-related mortality. Screening of anti-metastasis drugs often includes functional assays that examine cancer cell invasion inside a three-dimensional hydrogel that mimics the extracellular matrix (ECM). Here, we built a mechanically tuneable collagen hydrogel model to recapitulate cancer spreading into heterogeneous tumour stroma and monitored the three-dimensional invasion of highly malignant breast cancer cells, MDA-MB-231. Migration assays were carried out in the presence and the absence of drugs affecting four typical molecular mechanisms involved in cell migration, as well as under five ECMs with different biophysical properties. Strikingly, the effects of the drugs were observed to vary strongly with matrix mechanics and microarchitecture, despite the little dependence of the inherent cancer cell migration on the ECM condition. Specifically, cytoskeletal contractility-targeting drugs reduced migration speed in sparse gels, whereas migration in dense gels was retarded effectively by inhibiting proteolysis. The results corroborate the ability of cancer cells to switch their multiple invasion mechanisms depending on ECM condition, thus suggesting the importance of factoring in the biophysical properties of the ECM in anti-metastasis drug screenings.

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Profiling distinct mechanisms of tumour invasion for drug discovery: imaging adhesion, signalling and matrix turnover

Cited by 30 publications

References 111 publications

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

Systems microscopy approaches to understand cancer cell migration and metastasis

Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

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