Detection of Hypoxia in Cancer Models: Significance, Challenges, and Advances

Godet, Inês; Doctorman, Steven; Wu, Fan; Gilkes, Daniele M.

doi:10.3390/cells11040686

Cited by 69 publications

(42 citation statements)

References 136 publications

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“…In vitro, the presence of regions of hypoxia within the spheroid core of a pancreatic tumor [ 51 ], in MCF-7 cell-derived spheroids [ 40 , 52 ] and within the center of glioblastoma spheroids [ 53 ], are well characterized. In this study, the analysis of transcript levels suggests that PANC-1 cells grown as spheroid aggregates downregulate the respiratory complexes, as a result of hypoxia-driven metabolic adjustment.…”

Section: Discussionmentioning

confidence: 99%

Thermomagnetic Resonance Effect of the Extremely Low Frequency Electromagnetic Field on Three-Dimensional Cancer Models

Bergandi

Lucia

Grisolia

et al. 2022

IJMS

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In our recent studies, we have developed a thermodynamic biochemical model able to select the resonant frequency of an extremely low frequency electromagnetic field (ELF-EMF) specifically affecting different types of cancer, and we have demonstrated its effects in vitro. In this work, we investigate the cellular response to the ELF electromagnetic wave in three-dimensional (3D) culture models, which mimic the features of tumors in vivo. Cell membrane was modelled as a resistor–capacitor circuit and the specific thermal resonant frequency was calculated and tested on two-dimensional (2D) and three-dimensional (3D) cell cultures of human pancreatic cancer, glioblastoma and breast cancer. Cell proliferation and the transcription of respiratory chain and adenosine triphosphate synthase subunits, as well as uncoupling proteins, were assessed. For the first time, we demonstrate that an ELF-EMF hampers growth and potentiates both the coupled and uncoupled respiration of all analyzed models. Interestingly, the metabolic shift was evident even in the 3D aggregates, making this approach particularly valuable and promising for future application in vivo, in aggressive cancer tissues characterized by resistance to treatments.

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Section: Discussionmentioning

confidence: 99%

Thermomagnetic Resonance Effect of the Extremely Low Frequency Electromagnetic Field on Three-Dimensional Cancer Models

Bergandi

Lucia

Grisolia

et al. 2022

IJMS

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“…There is no unambiguous and uniform classification system. One of the possible explanations is that there is currently no agreement on the methods for studying tumor hypoxia in vitro or in vivo [ 56 , 60 ]. Therefore, there is an urgent need to standardize methods to recreate intratumoral hypoxia in the laboratory and detect intratumoral hypoxia in the clinic.…”

Section: Hypoxic Tumor Microenvironmentmentioning

confidence: 99%

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

et al. 2022

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Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

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“…TME is a dynamic and complex system around a tumor, which is composed of blood vessels, fibroblasts, extracellular matrix fibers, immune cells, and signaling molecules, supporting proliferation, metastasis, and therapy resistance of tumor cells [13] . The rapid proliferation of cancer cells and aberrant blood vessel formation create hypoxic conditions in malignant tumors.…”

Section: Hypoxic Tmementioning

confidence: 99%

Exosome secretion from hypoxic cancer cells reshapes the tumor microenvironment and mediates drug resistance

To¹,

Cho²

2022

Cancer Drug Resist

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Hypoxia is a common phenomenon in solid tumors as the poorly organized tumor vasculature cannot fulfill the increasing oxygen demand of rapidly expanding tumors. Under hypoxia, tumor cells reshape their microenvironment to sustain survival, promote metastasis, and develop resistance to therapy. Exosomes are extracellular vesicles secreted by most eukaryotic cells, including tumor cells. They are enriched with a selective collection of nucleic acids and proteins from the originating cells to mediate cell-to-cell communication. Accumulating evidence suggests that exosomes derived from tumor cells play critical roles in modulating the tumor microenvironment (TME). Hypoxia is known to stimulate the secretion of exosomes from tumor cells, thereby promoting intercellular communication of hypoxic tumors with the surrounding stromal tissues. Exosome-mediated signaling pathways under hypoxic conditions have been reported to cause angiogenesis, invasion, metastasis, drug resistance, and immune escape. Recently, the programmed cell death ligand-1 (PD-L1) has been reported to reside as a transmembrane protein in tumor exosomes. Exosomal PD-L1 was shown to suppress T cell effector function in the TME and cause drug resistance to immune checkpoint therapy. This review provides an update about the pivotal role of tumor-derived exosomes in drug resistance to chemotherapy and immunotherapy, particularly under hypoxic conditions. Emerging strategies that target the exosomes in the hypoxic TME to enhance the antitumor efficacy are discussed.

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Detection of Hypoxia in Cancer Models: Significance, Challenges, and Advances

Cited by 69 publications

References 136 publications

Thermomagnetic Resonance Effect of the Extremely Low Frequency Electromagnetic Field on Three-Dimensional Cancer Models

Thermomagnetic Resonance Effect of the Extremely Low Frequency Electromagnetic Field on Three-Dimensional Cancer Models

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Exosome secretion from hypoxic cancer cells reshapes the tumor microenvironment and mediates drug resistance

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