Modeling metastasis biology and therapy in real time in the mouse lung

Mendoza, Arnulfo; Hong, Saahoon; Osborne, Tanasa; Khan, Mohammed; Briggs, Josie P.; Eleswarapu, Ananth; Buquo, Lauren; Ren, Ling; Hewitt, Stephen M.; Dakir, El Habib; Garfield, Susan H.; Merlino, Glenn; Green, Jeffrey E.; Hunter, Kent W.; Wakefield, Lalage M.; Khanna, Chand

doi:10.1172/jci40252c1

Cited by 16 publications

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“…We examined the effects of SFK inhibition on the dormant-to-proliferative switch using an ex vivo pulmonary metastatic assay (PuMA) to observe the behavior of metastatic cells in real time in lung culture sections. In this assay, we tail-vein injected tumor cells into mice, with removal of the lungs 15 minutes later and culture of the lung sections in vitro (24). The PuMA assay recapitulated the in vivo increase in metastatic burden in fibrotic lungs compared with that seen in nonfibrotic lungs (Supplemental Figure 2B).…”

Section: Sfk Inhibition Prevents the Col1-induced Dormant-to-prolifermentioning

confidence: 90%

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Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells

et al. 2013

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Section: Sfk Inhibition Prevents the Col1-induced Dormant-to-prolifermentioning

confidence: 90%

“…The PuMA assay was performed as previously described (24), and details of this assay are provided in the Supplemental Methods.…”

Section: Inhibition Of Sfk With Azd0530mentioning

confidence: 99%

Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells

et al. 2013

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“…Studies have suggested that extravasation is a relatively rapid process (i.e., tumor cells extravasate 1-2 d following tail vein injection) (Cameron et al 2000;Mendoza et al 2010). However, tail vein assays involve injecting high numbers of tumor cells directly into the circulation.…”

Section: Clinical Evidence For Emt In Ctcsmentioning

confidence: 99%

Epithelial–mesenchymal plasticity in carcinoma metastasis

2013

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Tumor metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. Metastasis occurs through a series of steps: local invasion, intravasation, transport, extravasation, and colonization. A developmental program termed epithelial-mesenchymal transition (EMT) has been shown to play a critical role in promoting metastasis in epithelium-derived carcinoma. Recent experimental and clinical studies have improved our knowledge of this dynamic program and implicated EMT and its reverse program, mesenchymal-epithelial transition (MET), in the metastatic process. Here, we review the functional requirement of EMT and/or MET during the individual steps of tumor metastasis and discuss the potential of targeting this program when treating metastatic diseases.Epithelial and mesenchymal cell types have long been recognized by their unique cell morphology and organization in tissues. Epithelial cells form polarized sheets or layers of cells that are connected laterally via several types of cellular junctions, including adherens junctions, desmosomes, and tight junctions. In addition, epithelial cells anchor themselves to the underlying basement membrane via hemidesmosomes to maintain apical-basal polarity. Both desmosomes and hemidesmosomes further connect with the epithelial-specific cytokeratin intermediate filaments. In contrast, mesenchymal cells embed themselves inside the extracellular matrix (ECM) and rarely establish tight contact with neighboring cells. During specific embryonic morphogenesis processes such as mesoderm formation and neural crest development, epithelial cells can exhibit enormous plasticity and transit into a mesenchymal state by activating the epithelial-mesenchymal transition (EMT) program. After EMT, these cells lose their epithelial junctions and switch to producing vimentin filaments. The functional hallmark of the EMT program is to allow stationary epithelial cells to gain the ability to migrate and invade during developmental morphogenesis (Boyer and Thiery 1993;Hay 1995).Although epithelial cells convert into the mesenchymal state during developmental EMT, entering the EMT program is not necessarily an irreversible commitment, as evident during kidney tubule formation. These epithelial cells can activate a transitory EMT program and then undergo a reverse process called mesenchymal-epithelial transition (MET) to continue their differentiation paths (Thiery et al. 2009;Lim and Thiery 2012). In many instances, the identification of an epithelial versus a mesenchymal state can be relatively fluid, and a partial EMT/MET frequently occurs to fulfill unique developmental tasks. These dynamic EMT/MET events highlight the enormous flexibility of presumably differentiated cells during morphogenesis.In the past decade, an increasing number of studies have provided strong evidence for the reinitiation of the EMT developmental program in carcinoma progression and metastasis. This EMT program in tumor metastasis possesses many morpholog...

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“…Using a similar model, Gassman et al demonstrated that CXCL12, expressed in the endothelial cells of the liver blood vessels, interacted with CXCR4 expressed in the tumor cells, and promoted tumor cell adhesion to the liver blood vessels and extravasation into the liver [69]. A study in which the lungs were perfused and sections of tissue placed on agarose-based medium for up to 21 days, allowing the monitoring of metastatic tumor growth, showed that the survival of cells arriving in lung was the limiting step of metastatic efficiency [70]. In these models, the tissue architecture is maintained, with stromal cells and relevant ECM components.…”

Section: Study Of Metastasis In the Chamber Modelmentioning

confidence: 99%

Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model

Borgström¹,

Welsh²

2012

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Modeling metastasis biology and therapy in real time in the mouse lung

Abstract: In Figure 3E, the units provided for carbohydrate oxidation and fat oxidation were incorrect. The units for both should be g/d/kg 0.75 .The authors regret the error.

Cited by 16 publications

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Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells

Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells

Epithelial–mesenchymal plasticity in carcinoma metastasis

Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model

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