Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

Choi, Kyu Jin; Nam, Jae-Kyung; Kim, Jihee; Choi, Seo‐Hyun; Lee, Yoonjin

doi:10.1038/s12276-020-0439-4

Cited by 64 publications

(49 citation statements)

References 112 publications

(148 reference statements)

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“…EndMT is a transition process from an endothelial phenotype to a mesenchymal phenotype resembling a spindle-like shape, and increases the migration of metastatic cells [16,17]. EndMT contributes to the accumulation of CAFs and most CAFs are formed by EndMT [18].…”

Section: Introductionmentioning

confidence: 99%

Cancer-Associated Fibroblasts Differentiated by Exosomes Isolated from Cancer Cells Promote Cancer Cell Invasion

Kim

Sohn

Lee

et al. 2020

IJMS

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Cancer-associated fibroblasts (CAFs) in the cancer microenvironment play an essential role in metastasis. Differentiation of endothelial cells into CAFs is induced by cancer cell-derived exosomes secreted from cancer cells that transfer molecular signals to surrounding cells. Differentiated CAFs facilitate migration of cancer cells to different regions through promoting extracellular matrix (ECM) modifications. However, in vitro models in which endothelial cells exposed to cancer cell-derived exosomes secreted from various cancer cell types differentiate into CAFs or a microenvironmentally controlled model for investigating cancer cell invasion by CAFs have not yet been studied. In this study, we propose a three-dimensional in vitro cancer cell invasion model for real-time monitoring of the process of forming a cancer invasion site through CAFs induced by exosomes isolated from three types of cancer cell lines. The invasiveness of cancer cells with CAFs induced by cancer cell-derived exosomes (eCAFs) was significantly higher than that of CAFs induced by cancer cells (cCAFs) through physiological and genetic manner. In addition, different genetic tendencies of the invasion process were observed in the process of invading cancer cells according to CAFs. Our 3D microfluidic platform helps to identify specific interactions among multiple factors within the cancer microenvironment and provides a model for cancer drug development.

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Section: Introductionmentioning

confidence: 99%

Cancer-Associated Fibroblasts Differentiated by Exosomes Isolated from Cancer Cells Promote Cancer Cell Invasion

Kim

Sohn

Lee

et al. 2020

IJMS

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“…Ionizing radiation, a component of the standard of care for GBM, can induce mesenchymal features in GBM through NFkB activation [ 53 , 54 ]. NFkB may drive mesenchymal conversion by controlling the expression of genes associated with a mesenchymal program such as Signal Transducer and Activator of Transcription (STAT) 3 and CCAAT-enhancer-binding protein B (C/EBPB) [ 55 ]. NFkB is constitutively activated in glioma stem cell patient lines and GBM mouse models and has an essential role in controlling GBM pathobiology [ 56 , 57 , 58 , 59 ].…”

Section: The Identity Of the Tumor Cells In The Peritumoral Zonementioning

confidence: 99%

Residual Disease in Glioma Recurrence: A Dangerous Liaison with Senescence

Putavet

Keizer

2021

Cancers

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With a dismally low median survival of less than two years after diagnosis, Glioblastoma (GBM) is the most lethal type of brain cancer. The standard-of-care of surgical resection, followed by DNA-damaging chemo-/radiotherapy, is often non-curative. In part, this is because individual cells close to the resection border remain alive and eventually undergo renewed proliferation. These residual, therapy-resistant cells lead to rapid recurrence, against which no effective treatment exists to date. Thus, new experimental approaches need to be developed against residual disease to prevent GBM survival and recurrence. Cellular senescence is an attractive area for the development of such new approaches. Senescence can occur in healthy cells when they are irreparably damaged. Senescent cells develop a chronic secretory phenotype that is generally considered pro-tumorigenic and pro-migratory. Age is a negative prognostic factor for GBM stage, and, with age, senescence steadily increases. Moreover, chemo-/radiotherapy can provide an additional increase in senescence close to the tumor. In light of this, we will review the importance of senescence in the tumor-supportive brain parenchyma, focusing on the invasion and growth of GBM in residual disease. We will propose a future direction on the application of anti-senescence therapies against recurrent GBM.

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“…Furthermore, TEC can undergo Endothelial-Mesenchymal-Transition thereby giving rise to CAF and contributing to CAF enrichment in PDAC. In humans, this process seems to be mediated by inflammatory factors such as TNF-α [ 261 , 262 , 263 ].…”

Section: Heterogeneity Of the Stromal Compartment In Pdacmentioning

confidence: 99%

The Heterogeneity of the Tumor Microenvironment as Essential Determinant of Development, Progression and Therapy Response of Pancreatic Cancer

Wandmacher

Mehdorn

Sebens

2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at advanced stages and most anti-cancer therapies have failed to substantially improve prognosis of PDAC patients. As a result, PDAC is still one of the deadliest tumors. Tumor heterogeneity, manifesting at multiple levels, provides a conclusive explanation for divergent survival times and therapy responses of PDAC patients. Besides tumor cell heterogeneity, PDAC is characterized by a pronounced inflammatory stroma comprising various non-neoplastic cells such as myofibroblasts, endothelial cells and different leukocyte populations which enrich in the tumor microenvironment (TME) during pancreatic tumorigenesis. Thus, the stromal compartment also displays a high temporal and spatial heterogeneity accounting for diverse effects on the development, progression and therapy responses of PDAC. Adding to this heterogeneity and the impact of the TME, the microbiome of PDAC patients is considerably altered. Understanding this multi-level heterogeneity and considering it for the development of novel therapeutic concepts might finally improve the dismal situation of PDAC patients. Here, we outline the current knowledge on PDAC cell heterogeneity focusing on different stromal cell populations and outline their impact on PDAC progression and therapy resistance. Based on this information, we propose some novel concepts for treatment of PDAC patients.

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Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

Cited by 64 publications

References 112 publications

Cancer-Associated Fibroblasts Differentiated by Exosomes Isolated from Cancer Cells Promote Cancer Cell Invasion

Cancer-Associated Fibroblasts Differentiated by Exosomes Isolated from Cancer Cells Promote Cancer Cell Invasion

Residual Disease in Glioma Recurrence: A Dangerous Liaison with Senescence

The Heterogeneity of the Tumor Microenvironment as Essential Determinant of Development, Progression and Therapy Response of Pancreatic Cancer

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