scholarly journals Platelets and extracellular vesicles and their cross-talk with cancer

Blood ◽  
2021 ◽  
Author(s):  
Sophia Lazar ◽  
Lawrence E. Goldfinger
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Second Messengers ◽  
Inflammatory Cells ◽  
Surface Proteins ◽  
Non Coding Rnas ◽  
Promote Disease Progression ◽  
Mature Mrnas ◽  
Heterogeneous Size

Platelets play significant and varied roles in cancer progression, as detailed throughout this review series, via direct interactions with cancer cells as well as by long-range indirect interactions mediated by platelet releasates. Microvesicles (MV, also referred to as microparticles) released from activated platelets have emerged as major contributors to the platelet-cancer nexus. Interactions of platelet-derived MV (PMV) with cancer cells can promote disease progression through multiple mechanisms, but PMV also harbor anti-tumor functions. This complex relationship derives from the abilities of PMV both to bind to cancer cells as well as to non-transformed cells in the tumor microenvironment, and to transfer platelet-derived contents to the target cell, each of which can have stimulatory or modulatory effects. MV are extracellular vesicles of heterogeneous size, ranging from 100 nm to 1 µm in diameter, shed by living cells by outward budding of the plasma membrane, entrapping local cytosolic contents in an apparently stochastic manner. Hence, PMV are encapsulated by a lipid bilayer harboring surface proteins and lipids mirroring the platelet exterior, with internal components including platelet-derived mature mRNAs and pre-mRNAs, microRNAs (miRNAs) and other non-coding RNAs, proteins, second messengers, and mitochondria. Each of these elements engages in established and putative PMV functions in cancer. In addition, PMV contribute to cancer co-morbidities due to their roles in coagulation and thrombosis, and via interactions with inflammatory cells. However, separating effects of PMV from those of platelets in cancer contexts continues to be a major hurdle (Figure 1). This review will summarize our emerging understanding of the complex roles of PMV in the development and progression of cancer and cancer co-morbidities.

scholarly journals Snail Overexpression Alters the microRNA Content of Extracellular Vesicles Released from HT29 Colorectal Cancer Cells and Activates Pro-Inflammatory State In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 172
Author(s):  
Izabela Papiewska-Pająk ◽  
Patrycja Przygodzka ◽  
Damian Krzyżanowski ◽  
Kamila Soboska ◽  
Izabela Szulc-Kiełbik ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Microrna Profile ◽  
Inflammatory State ◽  
Metastatic Process

During metastasis, cancer cells undergo phenotype changes in the epithelial-mesenchymal transition (EMT) process. Extracellular vesicles (EVs) released by cancer cells are the mediators of intercellular communication and play a role in metastatic process. Knowledge of factors that influence the modifications of the pre-metastatic niche for the migrating carcinoma cells is important for prevention of metastasis. We focus here on how cancer progression is affected by EVs released from either epithelial-like HT29-cells or from cells that are in early EMT stage triggered by Snail transcription factor (HT29-Snail). We found that EVs released from HT29-Snail, as compared to HT29-pcDNA cells, have a different microRNA profile. We observed the presence of interstitial pneumonias in the lungs of mice injected with HT29-Snail cells and the percent of mice with lung inflammation was higher after injection of HT29-Snail-EVs. Incorporation of EVs released from HT29-pcDNA, but not released from HT29-Snail, leads to the increased secretion of IL-8 from macrophages. We conclude that Snail modifications of CRC cells towards more invasive phenotype also alter the microRNA cargo of released EVs. The content of cell-released EVs may serve as a biomarker that denotes the stage of CRC and EVs-specific microRNAs may be a target to prevent cancer progression.

The cholesterol metabolite 27-hydroxycholesterol increases the secretion of extracellular vesicles which promote breast cancer progression

Endocrinology ◽  
2021 ◽  
Author(s):  
Amy E Baek ◽  
Natalia Krawczynska ◽  
Anasuya Das Gupta ◽  
Svyatoslav Victorovich Dvoretskiy ◽  
Sixian You ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Myeloid Cells ◽  
Breast Cancer Progression ◽  
Label Free ◽  
Tumor Growth And Metastasis ◽  
Promote Breast Cancer

Abstract Cholesterol has been implicated in the clinical progression of breast cancer, a disease that continues to be the most commonly diagnosed cancer in women. Previous work has identified the cholesterol metabolite, 27-hydroxycholesterol (27HC), as a major mediator of the effects of cholesterol on breast tumor growth and progression. 27HC can act as an estrogen receptor (ER) modulator to promote the growth of ERα+ tumors, and a liver x receptor (LXR) ligand in myeloid immune cells to establish an immune-suppressive program. In fact, the metastatic properties of 27HC require the presence of myeloid cells, with neutrophils (PMNs) being essential for the increase in lung metastasis in murine models. In an effort to further elucidate the mechanisms by which 27HC alters breast cancer progression, we made the striking finding that 27HC promoted the secretion of extracellular vesicles (EVs), a diverse assortment of membrane bound particles that include exosomes. The resulting EVs had a size distribution that was skewed slightly larger, compared to EVs generated by treating cells with vehicle. The increase in EV secretion and size was consistent across three different subtypes: primary murine PMNs, RAW264.7 monocytic cells and 4T1 murine mammary cancer cells. Label-free analysis of 27HC-EVs indicated that they had a different metabolite composition to those from vehicle-treated cells. Importantly, 27HC-EVs from primary PMNs promoted tumor growth and metastasis in two different syngeneic models, demonstrating the potential role of 27HC induced EVs in the progression of breast cancer. EVs from PMNs were taken up by cancer cells, macrophages and PMNs, but not T cells. Since EVs did not alter proliferation of cancer cells, it is likely that their pro-tumor effects are mediated through interactions with myeloid cells. Interestingly, RNA-seq analysis of tumors from 27HC-EV treated mice do not display significantly altered transcriptomes, suggesting that the effects of 27HC-EVs occur early on in tumor establishment and growth. Future work will be required to elucidate the mechanisms by which 27HC increases EV secretion, and how these EVs promote breast cancer progression. Collectively however, our data indicate that EV secretion and content can be regulated by a cholesterol metabolite, which may have detrimental effects in terms of disease progression, important findings given the prevalence of both breast cancer and hypercholesterolemia.

scholarly journals Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression

Tumor Biology ◽  
2018 ◽  
Vol 40 (2) ◽  
pp. 101042831875620 ◽  
Author(s):  
Filipa Lopes-Coelho ◽  
Sofia Gouveia-Fernandes ◽  
Jacinta Serpa
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Inflammatory Cells ◽  
Metabolic Adaptation ◽  
Metabolic Cooperation ◽  
Metabolic Remodeling ◽  
Organ Tissue ◽  
Cancerous Cells

The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

scholarly journals Extracellular Vesicles in Cancer Metabolism: Implications for Cancer Diagnosis and Treatment

2021 ◽  
Vol 20 ◽  
pp. 153303382110378
Author(s):  
Qian Zhang ◽  
Xiangling Yang ◽  
Huanliang Liu
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Diagnosis ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Bioactive Molecules ◽  
Diagnosis And Treatment ◽  
Existing Problems ◽  
Non Coding Rnas

Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.

scholarly journals Cancer associated-fibroblast-derived exosomes in cancer progression

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chao Li ◽  
Adilson Fonseca Teixeira ◽  
Hong-Jian Zhu ◽  
Peter ten Dijke
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Chemotherapy Resistance ◽  
Cell Types ◽  
Cancer Therapies ◽  
Cancer Associated Fibroblast

AbstractTo identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

scholarly journals Involvement of Extracellular Vesicles in Vascular-Related Functions in Cancer Progression and Metastasis

2019 ◽  
Vol 20 (10) ◽  
pp. 2584 ◽  
Author(s):  
Shinsuke Kikuchi ◽  
Yusuke Yoshioka ◽  
Marta Prieto-Vila ◽  
Takahiro Ochiya
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Cell Communication ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Patients With Cancer ◽  
Tumor Environment ◽  
Endothelial To Mesenchymal Transition

The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.

scholarly journals Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Into Extracellular Vesicles

2020 ◽  
Author(s):  
Shun Wilford Tse ◽  
Chee Fan Tan ◽  
Jung Eun Park ◽  
JebaMercy Gnanasekaran ◽  
Nikhil Gupta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Membrane Trafficking ◽  
Tumour Cell ◽  
Host Immunity ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Functional Clustering

Abstract Background: Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that oxygen starvation in developing tumours induces specific hypoxia-sensitive proteins for packing into small EVs to modulate its microenvironment for cancer progression and enhance malignancy. Methods: We employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia-sensitive EVs proteins (HSEPs) in hypoxic A549 lung adenocarcinoma cells derived small EVs (<200 nm). Proteomics data mining and pathway analysis were used to reveal potential roles of the HSEPs in enhancing tumour cell progression and in modulating host immunity. Functional clustering was applied to study enhanced EVs biogenesis and secretion in hypoxic cancer cells. Subsequent biochemical functional assays were performed in A549 and H1299 lung cancer cells to validate the hypoxic cancer-derived EVs in promoting cancer progression.Results: Results revealed that hypoxia stimulated cancer cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Conclusion: Together, these data indicate that lung cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may therefore offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.

scholarly journals Molecular insights and clinical impacts of extracellular vesicles in cancer

2021 ◽  
Vol 2 (15) ◽  
Author(s):  
Kittinun Leetanaporn ◽  
Jitti Hanprasertpong ◽  
Raphatphorn Navakanitworakul
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Biology ◽  
Cell Communication ◽  
Research Direction ◽  
Cancer Development ◽  
The Novel ◽  
Membrane Bound ◽  
Non Coding Rnas ◽  
Intercellular Communications

Cell-to-cell communication is a pivotal aspect of cancer biology. Recently, extracellular vesicles (EVs) have been shown to play essential roles in intercellular communications between cancer cells and the surrounding microenvironment owing to cancer development. EVs are small membrane-bound vesicles secreted by various cells containing proteins, lipids, mRNAs, and non-coding RNAs (microRNAs and long non-coding RNAs), which contribute to cancer cell development and progression. Here, we provide an overview of current research direction on EVs, especially biomolecules in EVs, and also point out the novel diagnostics, monitoring, predicting, and therapeutic aspects using EVs against cancer.

Crosstalk of long non-coding RNAs and EMT: Searching the missing pieces of an incomplete puzzle for lung cancer therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Md Shahinozzaman ◽  
Sima Orouei ◽  
Vahideh Zarrin ◽  
Kiavash Hushmandi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
Life Threatening ◽  
Non Coding Rnas ◽  
Potential Factors

Background: Lung cancer is considered to be the first place among the cancer-related deaths worldwide and demands novel strategies in the treatment of this life-threatening disorder. The aim of this review is to explore regulation of epithelial-to-mesenchymal transition (EMT) by long non-coding RNAs (lncRNAs) in lung cancer. Introduction: LncRNAs can be considered as potential factors for targeting in cancer therapy, since they regulate a bunch of biological processes, e.g. cell proliferation, differentiation and apoptosis. The abnormal expression of lncRNAs occurs in different cancer cells. On the other hand, epithelial-to-mesenchymal transition (EMT) is a critical mechanism participating in migration and metastasis of cancer cells. Method: Different databases including Googlescholar, Pubmed and Sciencedirect were used for collecting articles using keywords such as “LncRNA”, “EMT”, and “Lung cancer”. Result: There are tumor-suppressing lncRNAs that can suppress EMT and metastasis of lung cancer cells. Expression of such lncRNAs undergoes down-regulation in lung cancer progression and restoring their expression is of importance in suppressing lung cancer migration. There are tumor-promoting lncRNAs triggering EMT in lung cancer and enhancing their migration. Conclusion: LncRNAs are potential regulators of EMT in lung cancer, and targeting them, both pharmacologically and genetically, can be of importance in controlling migration of lung cancer cells.

scholarly journals Glypican-1 Level Is Elevated in Extracellular Vesicles Released from MC38 Colon Adenocarcinoma Cells Overexpressing Snail

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1585
Author(s):  
Izabela Papiewska-Pająk ◽  
Damian Krzyżanowski ◽  
Maria Katela ◽  
Romain Rivet ◽  
Sylwia Michlewska ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Protein Level ◽  
Colon Adenocarcinoma ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Colon Adenocarcinoma Cells

The transcription factor Snail triggers epithelial-to-mesenchymal transition (EMT), endowing cancer cells with invasive properties during tumor progression. Extracellular vesicles (EVs) released from cancer cells at various stages of cancer progression are known to influence the tumor pre-metastatic niche and metastatic potential. The aim of this study was to analyze the effect of Snail on murine colon adenocarcinoma cells (MC38 line) and on the characteristics of their EVs. Stable clones of Snail-overexpressing MC38 cells were investigated in vitro versus Mock cells. Increased expression of matrix metalloproteinase MMP-14 and augmented activity of MMP-9 and -14 were observed in Snail-MC38 cells. There was no change in the transcriptomic profile of proteoglycans in Snail-MC38 cells; however, the protein level of Glypican-1 (GPC1) was enhanced in EVs released from those cells. Our finding that GPC1 protein level was enhanced in EVs released from MC38 cells that overexpressed Snail and were in an early EMT stage might explain the specificity of the GPC1 biomarker in colon cancer diagnosis. Further, our data suggest that Snail, by changing the level of GPC1 on EVs released by colon cancer cells, may affect the generation of a distant premetastatic niche and metastatic organotropism in colon adenocarcinoma.

Sign in / Sign up

Export Citation Format

Share Document