Microtentacles Tip the Balance of Cytoskeletal Forces in Circulating Tumor Cells

Matrone, Michael A.; Whipple, Rebecca A.; Balzer, Eric M.; Martin, Stuart S.

doi:10.1158/0008-5472.can-10-1569

Cited by 61 publications

(69 citation statements)

References 30 publications

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“…Expression of Twist1 or Snail1 in human mammary epithelial cells promotes microtentacle formation in detached cells, suggesting that EMT could aid CTC survival via microtenacle-based attachment of CTCs to leukocytes, platelets, and endothelium ( Fig. 3; Matrone et al 2010a). …”

Section: Experimental 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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Section: Experimental Evidence For Emt In Ctcsmentioning

confidence: 99%

Epithelial–mesenchymal plasticity in carcinoma metastasis

2013

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“…The morphology of cell is delicately controlled by expansion force of microtubules and counter-expansion force of actin, which reach a balance to stabilize cell shape (Ingber 2003). EMT-induced vimentin expression that tips balance of the cytoskeletal force toward microtubule stabilization and actin depolymerization promotes microtentacles formation, which in turn bestows more aggressive features on CTCs, such as deformability, ability to aggregate homo-and heterotypically, and more efficient intravascular retention (Matrone et al 2010).…”

Section: Does Emt Bridge Ctcs and Circulating Cancer Stem Cellsmentioning

confidence: 99%

Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

Sun

Yang

Zhou

et al. 2011

J Cancer Res Clin Oncol

164

137

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“…Its overexpression has been observed in several human tumor cells (Matrone et al, 2010) and generally in cells with growing and metastatic phenotype (DutschWicherek, 2010) akin to overangiogenic MMECs, but it is not defined as an oncogene. VIM is highly positive in MM BM neovessels and, at variance with MGECs, it is disassembled in the cytoplasm and cellular protrusions of MMECs.…”

Section: Angiogenic Proteins Of Mmecs S Berardi Et Almentioning

confidence: 99%

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

et al. 2011

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Bone marrow (BM) angiogenesis has an important role in the initiation and progression of multiple myeloma (MM). We looked at novel mechanisms of vessel formation in patients with MM through a comparative proteomic analysis between BM endothelial cells (ECs) of patients with active MM (MMECs) and ECs of patients with monoclonal gammopathy of undetermined significance (MGECs) and of subjects with benign anemia (normal ECs). Four proteins were found overexpressed in MMECs: filamin A, vimentin, a-crystallin B and 14-3-3f/d protein, not yet linked to overangiogenic phenotype. These proteins gave a typical distribution in the BM of MM patients and in MMECs versus MGECs, plausibly according to a different functional state. Their expression was enhanced by vascular endothelial growth factor, fibroblast growth factor 2, hepatocyte growth factor and MM plasma cell conditioned medium in step with enhancement of MMEC angiogenesis. Their silencing RNA knockdown affected critical MMEC angiogenesis-related functions, such as spreading, migration and tubular morphogenesis. A gradual stabilization of 14-3-3f/d protein was observed, with transition from normal ECs to MGECs and MMECs that may be a critical step for the angiogenic switch in MMECs and maintenance of the cell overangiogenic phenotype. These proteins were substantially impacted by anti-MM drugs, such as bortezomib, lenalidomide and panobinostat. Results suggest that these four proteins could be new targets for the antiangiogenic management of MM patients.

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Microtentacles Tip the Balance of Cytoskeletal Forces in Circulating Tumor Cells

Cited by 61 publications

References 30 publications

Epithelial–mesenchymal plasticity in carcinoma metastasis

Epithelial–mesenchymal plasticity in carcinoma metastasis

Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

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