Direct visualization of the phenotype of hypoxic tumor cells at single cell resolution in vivo using a new hypoxia probe

Wang, Yarong; Wang, Haoxuan; Li, Jiufeng; Entenberg, David; Xue, Alice; Wang, Weigang; Condeelis, John S.

doi:10.1080/21659087.2016.1187803

Cited by 25 publications

(36 citation statements)

References 74 publications

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“…This places hypoxic cells into the slow migratory phenotype associated with invasion and dissemination as observed previously [35]. Concordant with this, hypoxic cells were also observed to have dramatically increased invadopodia with degradative activity and be more chemotactic toward flowing blood vessels with which hypoxic cells were found to associate in vivo [6] (Figure 1). …”

Section: Hypoxia Motility and Directionality In The Primary Tumorsupporting

confidence: 84%

“…Sustained hypoxia in a growing tumor was described as being associated with a clinically aggressive phenotype, increased invasive capacity, perifocal tumor cell spreading, regional and distant dissemination, and resistance to different therapies [4,5]. However, hypoxia can also induce growth arrest, cause cell death, decrease motility speed while increasing invasiveness and directionality [6], and induce a dormancy-like program [7]. …”

Section: Hypoxia In Cell Fate and Cancermentioning

confidence: 99%

“…Recognizing these chromophore limitations, one group has developed a fluorescence resonance energy transfer (FRET)-based biosensor called FluBO using a combination of YFP and a avin-binding fluorescent protein [89]. Additionally, another study used mCherry, which is not dependent on oxygen for folding and fluorescence [6]. Although these reporters allow the tracking of the motility and invasive phenotypes of hypoxic cells with single cell resolution, only two of the studies utilizing these in vivo probes [6,85] analyzed migration and invasion of tumor cells.…”

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

“…Additionally, another study used mCherry, which is not dependent on oxygen for folding and fluorescence [6]. Although these reporters allow the tracking of the motility and invasive phenotypes of hypoxic cells with single cell resolution, only two of the studies utilizing these in vivo probes [6,85] analyzed migration and invasion of tumor cells.…”

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

“…The discrepancies raised above were resolved using intravital imaging [6] as this study was the first to directly visualize the motility of hypoxic tumor cells, with single-cell resolution, in living tissue. The authors found that hypoxic cells show dramatically reduced migration speeds (~24 mm/h) compared to normoxic cells (~66 mm/h).…”

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

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The Different Routes to Metastasis via Hypoxia-Regulated Programs

Nobre

Entenberg

Wang

et al. 2018

Trends in Cell Biology

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Hypoxia is linked to metastasis; however, how it affects metastatic progression is not clear due to limited consensus in the literature. We posit that this lack of consensus is due to hypoxia being studied using different approaches, such as in vitro, primary tumor, or metastasis assays in an isolated manner. Here, we review the pros and cons of in vitro hypoxia assays, highlight in vivo studies that inform on physiological hypoxia, and review the evidence that primary tumor hypoxia might influence the fate of disseminated tumor cells (DTCs) in secondary organs. Our analysis suggests that consensus can be reached by using in vivo methods of study, which also allow better modeling of how hypoxia affects DTC fate and metastasis.

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Section: Hypoxia Motility and Directionality In The Primary Tumorsupporting

confidence: 84%

Section: Hypoxia In Cell Fate and Cancermentioning

confidence: 99%

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

Section: Hypoxia Motility and Directionality In The Primary Tumormentioning

confidence: 99%

See 3 more Smart Citations

The Different Routes to Metastasis via Hypoxia-Regulated Programs

Nobre

Entenberg

Wang

et al. 2018

Trends in Cell Biology

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Frontiers in intravital multiphoton microscopy of cancer

2019

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Background Cancer is a highly complex disease, which involves the cooperation of tumor cells with multiple types of host cells and the extracellular matrix. Cancer studies that rely solely on static measurements of individual cell types are insufficient to dissect this complexity. In the last two decades, intravital microscopy has established itself as a powerful technique that can significantly improve our understanding of cancer by revealing the dynamic interactions governing cancer initiation, progression, and treatment effects in living animals. This review focuses on intravital multiphoton microscopy (IV‐MPM) applications in mouse models of cancer. Recent findings IV‐MPM studies have already enabled a deeper understanding of the complex events occurring in cancer at the molecular, cellular, and tissue levels. Multiple cell types present in different tissues influence cancer cell behavior via activation of distinct signaling pathways. As a result, the boundaries in the field of IV‐MPM are continuously being pushed to provide an integrated comprehension of cancer. We propose that optics, informatics, and cancer (cell) biology are coevolving as a new field. We have identified four emerging themes in this new field. First, new microscopy systems and image processing algorithms are enabling the simultaneous identification of multiple interactions between the tumor cells and the components of the tumor microenvironment. Second, techniques from molecular biology are being exploited to visualize subcellular structures and protein activities within individual cells of interest and relate those to phenotypic decisions, opening the door for “in vivo cell biology”. Third, combining IV‐MPM with additional imaging modalities or omics studies holds promise for linking the cell phenotype to its genotype, metabolic state, or tissue location. Finally, the clinical use of IV‐MPM for analyzing efficacy of anticancer treatments is steadily growing, suggesting a future role of IV‐MPM for personalized medicine. Conclusion IV‐MPM has revolutionized visualization of tumor‐microenvironment interactions in real time. Moving forward, incorporation of novel optics, automated image processing, and omics technologies in the study of cancer biology, will not only advance our understanding of the underlying complexities but will also leverage the unique aspects of IV‐MPM for clinical use.

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Fibronectin assembly regulates lumen formation in breast acini

Magdaleno

House

Pawar

et al. 2021

J of Cellular Biochemistry

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Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that selfassembles into FN fibrils, forming a FN matrix contributing to the stiffness of the ECM. Stromal FN stiffness in cancer has been shown to impact epithelial functions such as migration, cancer metastasis, and epithelial-to-mesenchymal transition. The role of the FN matrix of epithelial cells in driving such processes remains less well understood and is the focus of this study. Hypoxia, defined by low oxygen tension (<5%) is one of the hallmarks of tumor microenvironments impacting fibril reorganization in stromal and epithelial cells. Here, using the MCF10 breast epithelial progression series of cell lines encompassing normal, preinvasive, and invasive states, we show that FN fibril formation decreases during hypoxia, coinciding with a decrease in migratory potential of these cells. Conversely, we find that FN fibril disruption during three-dimensional acinar growth of normal breast cells resulted in acinar luminal filling. Our data also demonstrates that the luminal filling upon fibril disruption in untransformed MCF10A cells results in a loss of apicobasal polarity, characteristic of pre-invasive and invasive breast cell lines MCF10AT and MCF10 DCIS.com. Overall this is the first study that relates fibrilmediated changes in epithelial cells as critical players in lumen clearing of breast acini and maintenance of the untransformed growth characteristic.

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Direct visualization of the phenotype of hypoxic tumor cells at single cell resolution in vivo using a new hypoxia probe

Cited by 25 publications

References 74 publications

The Different Routes to Metastasis via Hypoxia-Regulated Programs

The Different Routes to Metastasis via Hypoxia-Regulated Programs

Frontiers in intravital multiphoton microscopy of cancer

Fibronectin assembly regulates lumen formation in breast acini

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