Pre-metastatic Niche Formation in Different Organs Induced by Tumor Extracellular Vesicles

Dong, Qi; Li, Xue; Cheng, Ke; Sheng, Jiahao; Kong, Jing; Liu, Tingjiao

doi:10.3389/fcell.2021.733627

Cited by 67 publications

(42 citation statements)

References 74 publications

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“…Remodeling of the ECM, driven by proteolytic enzymes (such as matrix metalloproteinases) [ 2 ], by enzymes that control the modification and cross-linking of extracellular matrix proteins (such as lysyloxidases (LOX)) [ 3 ], results in increased stiffness and altered ECM composition. Tumor cells also secrete extracellular vesicles with nucleic acids, lipids and proteins, which can participate in tumor progression and behavior, including tumor environment remodeling, fibroblast activation, angiogenesis, immunomodulation or the establishment of pre-metastatic niches [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Functional Role of Extracellular Matrix Proteins in Cancer

Popova

Jücker

2022

Cancers

129

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The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.

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Section: Introductionmentioning

confidence: 99%

The Functional Role of Extracellular Matrix Proteins in Cancer

Popova

Jücker

2022

Cancers

129

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“…One of the key factors that control CTC acceptance and possible micrometastasis formation is induction and stimulation of the supportive microenvironment (called premetastatic niche [263]) in distance organs by primary tumour [264]. Tumour cells display an ability to selectively modify the microenvironment of distant organs via extracellular vehicles (e.g., exomes).…”

Section: Effect Of Curcumin and Flavonoid Applications On Emt And Metastasis Formationmentioning

confidence: 99%

“…Numerous high-impact studies imply that tumour exosomes strongly support tumourgenesis and metastatic formation [264]. Ma et al reported that exosomes isolated from NSCLC patients displayed significantly higher levels of some miRNAs (e.g., miR-3157-3p, miR-3613-5p, and miR-3921) against healthy controls [266].…”

Section: Effect Of Curcumin and Flavonoid Applications On Emt And Metastasis Formationmentioning

confidence: 99%

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design

et al. 2021

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Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death. This review discusses the impact of NSCLC therapy strategies based on a meta-analysis of clinical studies. In addition, possible therapeutic strategies for repression when standard methods fail, such as the administration of low-toxicity natural anticancer agents targeting these phenomena (curcumin and flavonoids), are also discussed. These strategies are presented in the context of key mechanisms of tumour biology with a strong influence on CTC spread and metastasis (mechanisms related to tumour-associated and -infiltrating cells, epithelial–mesenchymal transition, and migration of cancer cells).

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“…Mexo secreted by highly metastatic melanoma cells are able to recruit bone marrow progenitor cells toward a pro-vasculogenic phenotype in the metastatic niche, mainly through MET signalling [ 95 , 96 , 97 ]. Therefore, we can hypothesize that Mexo initially promote angiogenesis to sustain tumour, then migrate to secondary sites to initiate PMN, to finally promote invasion and metastatic colonization to distant sites [ 98 ] ( Figure 2 ). Similar roles could be hypothesized also for acidic and hypoxic Mexo.…”

Section: How Acidity and Hypoxia Modulate Melanoma Progression Through Mexomentioning

confidence: 99%

Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Boussadia

Gambardella

Mattei

et al. 2021

Cells

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The mechanisms of melanoma progression have been extensively studied in the last decade, and despite the diagnostic and therapeutic advancements pursued, malignant melanoma still accounts for 60% of skin cancer deaths. Therefore, research efforts are required to better define the intercellular molecular steps underlying the melanoma development. In an attempt to represent the complexity of the tumour microenvironment (TME), here we analysed the studies on melanoma in acidic and hypoxic microenvironments and the interactions with stromal and immune cells. Within TME, acidity and hypoxia force melanoma cells to adapt and to evolve into a malignant phenotype, through the cooperation of the tumour-surrounding stromal cells and the escape from the immune surveillance. The role of tumour exosomes in the intercellular crosstalk has been generally addressed, but less studied in acidic and hypoxic conditions. Thus, this review aims to summarize the role of acidic and hypoxic microenvironment in melanoma biology, as well as the role played by melanoma-derived exosomes (Mexo) under these conditions. We also present a perspective on the characteristics of acidic and hypoxic exosomes to disclose molecules, to be further considered as promising biomarkers for an early detection of the disease. An update on the use of exosomes in melanoma diagnosis, prognosis and response to treatment will be also provided and discussed.

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Pre-metastatic Niche Formation in Different Organs Induced by Tumor Extracellular Vesicles

Cited by 67 publications

References 74 publications

The Functional Role of Extracellular Matrix Proteins in Cancer

The Functional Role of Extracellular Matrix Proteins in Cancer

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design

Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

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