scholarly journals Extracellular Vesicle Membrane-Associated Proteins: Emerging Roles in Tumor Angiogenesis and Anti-Angiogenesis Therapy Resistance

2020 ◽  
Vol 21 (15) ◽  
pp. 5418 ◽  
Author(s):  
Song Yi Ko ◽  
Honami Naora
Keyword(s):  
Tumor Angiogenesis ◽  
Therapy Resistance ◽  
Extracellular Vesicle ◽  
Biological Functions ◽  
Vesicle Membrane ◽  
Angiogenic Therapy ◽  
Anti Cancer ◽  
Associated Proteins ◽  
Tumor Growth And Metastasis ◽  
Prime Target

The tumor vasculature is essential for tumor growth and metastasis, and is a prime target of several anti-cancer agents. Increasing evidence indicates that tumor angiogenesis is stimulated by extracellular vesicles (EVs) that are secreted or shed by cancer cells. These EVs encapsulate a variety of biomolecules with angiogenic properties, and have been largely thought to stimulate vessel formation by transferring this luminal cargo into endothelial cells. However, recent studies have revealed that EVs can also signal to recipient cells via proteins on the vesicular surface. This review discusses and integrates emerging insights into the diverse mechanisms by which proteins associate with the EV membrane, the biological functions of EV membrane-associated proteins in tumor angiogenesis, and the clinical significance of these proteins in anti-angiogenic therapy.

scholarly journals Normalizing Tumor Vasculature to Reduce Hypoxia, Enhance Perfusion, and Optimize Therapy Uptake

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4444
Author(s):  
Kathy Matuszewska ◽  
Madison Pereira ◽  
Duncan Petrik ◽  
Jack Lawler ◽  
Jim Petrik
Keyword(s):  
Tumor Angiogenesis ◽  
Clinical Success ◽  
Tumor Hypoxia ◽  
Lymphatic Vessels ◽  
Therapy Resistance ◽  
Therapeutic Area ◽  
Comprehensive Understanding ◽  
Angiogenic Therapy ◽  
Tumor Growth And Metastasis ◽  
And Function

A basic requirement of tumorigenesis is the development of a vascular network to support the metabolic requirements of tumor growth and metastasis. Tumor vascular formation is regulated by a balance between promoters and inhibitors of angiogenesis. Typically, the pro-angiogenic environment created by the tumor is extremely aggressive, resulting in the rapid vessel formation with abnormal, dysfunctional morphology. The altered morphology and function of tumor blood and lymphatic vessels has numerous implications including poor perfusion, tissue hypoxia, and reduced therapy uptake. Targeting tumor angiogenesis as a therapeutic approach has been pursued in a host of different cancers. Although some preclinical success was seen, there has been a general lack of clinical success with traditional anti-angiogenic therapeutics as single agents. Typically, following anti-angiogenic therapy, there is remodeling of the tumor microenvironment and widespread tumor hypoxia, which is associated with development of therapy resistance. A more comprehensive understanding of the biology of tumor angiogenesis and insights into new clinical approaches, including combinations with immunotherapy, are needed to advance vascular targeting as a therapeutic area.

scholarly journals The role of tumor-derived exosomes in tumor angiogenesis and tumor progression

2019 ◽  
Vol 32 (4) ◽  
pp. 193-202 ◽  
Author(s):  
Alicja Gluszko ◽  
Shafaq M. Mirza ◽  
Katarzyna Piszczatowska ◽  
Ireneusz Kantor ◽  
Marta Struga ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
The Body ◽  
Term Survival ◽  
Waste Products ◽  
Angiogenic Therapy ◽  
Anti Cancer ◽  
Tumor Growth And Metastasis ◽  
Communication Pathway ◽  
Cancerous Cells

Abstract Exosomes, belonging to the group of extracellular bodies, are released by healthy as well as cancerous cells and serve as a communication pathway. Tumor-derived exosomes (TEX) possess the capacity to reprogram the function of normal cells owing to their genetic and molecular cargo. Such exosomes target endothelial cells (among others) in the tumor microenvironment to promote angiogenesis. Blood supply is essential in solid tumor growth and metastasis. The potential of pro-angiogenic changes is enhanced by an increased amount of circulating tumor-derived exosomes in the body fluids of cancer patients. A vascular network is important, since the proliferation, as well as the metastatic spread of cancer cells depends on an adequate supply of oxygen and nutrients, and the removal of waste products. New blood vessels and lymphatic vessels are formed through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. Thousands of patients have received anti-angiogenic therapy to date. Despite their theoretical efficacy, anti-angiogenic treatments have not proved beneficial in terms of long-term survival. Tumor-derived exosomes carrying pro-angiogenic factors might be a target for new anti-cancer therapy.

Circadian rhythms, sleep, and anti-cancer treatments

2018 ◽  
Author(s):  
Pasquale F. Innominato ◽  
David Spiegel
Keyword(s):  
Quality Of Life ◽  
Circadian Rhythms ◽  
Biological Functions ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Timing System ◽  
Physical Wellbeing ◽  
Circadian Timing System ◽  
Chemotherapy Agents

The circadian timing system temporally regulates biological functions relevant for psycho-physical wellbeing, spanning all the systems related to health. Hence, disruption of circadian rhythms, along with sleep cycles, is associated with the development of several diseases, including cancer. Moreover, altered circadian and sleep functions negatively impact on cancer patients’ quality of life and survival, above and beyond known determinants of outcome. This alteration can occur as a consequence of cancer, but also of anti-cancer treatments. Indeed, circadian rhythms govern also the ability of detoxifying chemotherapy agents across the 24 hours. Hence, adapting chemotherapy delivery to the molecular oscillations in relevant drug pathways can decrease toxicity to healthy cells, while increasing the number of cancer cells killing. This chronomodulated chemotherapy approach, together with the maintenance of proper circadian function throughtout the whole disease challenge, would finally result in safer and more active anticancer treatments, and in patients experiencing better quality and quantity of life.

scholarly journals Extracellular vesicle‐mediated endothelial apoptosis and EV‐associated proteins correlate with COVID‐19 disease severity

2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Balaji Krishnamachary ◽  
Christine Cook ◽  
Ashok Kumar ◽  
Leslie Spikes ◽  
Prabhakar Chalise ◽  
...  
Keyword(s):  
Disease Severity ◽  
Extracellular Vesicle ◽  
Endothelial Apoptosis ◽  
Associated Proteins

scholarly journals AB0080 A SYSTEM-LEVEL APPROACH IDENTIFIES A CRITICAL REGULATOR OF CHONDROSARCOMA PROGRESSION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1340.3-1340
Author(s):  
H. Kim ◽  
Y. Cho ◽  
J. H. Kim
Keyword(s):  
Histological Grade ◽  
System Level ◽  
Clinical Approach ◽  
Cancer Therapies ◽  
Functional Roles ◽  
Network Analyses ◽  
Molecular Events ◽  
Anti Cancer ◽  
Tumor Growth And Metastasis ◽  
Chemotherapy Agents

Background:Chondrosarcomas are cartilaginous tumors that constitute one-third of skeletal system cancers. Chondrosarcomas are capable of transitioning to highly metastatic and treatment-refractory states, resulting in significant patient mortality. However, the molecular events accompanying this behavior remain unknown.Objectives:We aimed to uncover the molecular pathway underlying such tumor progression that confers a higher malignancy to chondrosarcoma.Methods:We conducted unsupervised gene co-expression network analyses using transcriptomes of patients with chondrosarcoma and extracted a characteristic transcription network underlying chondrosarcoma malignancy. By implementing a system-level upstream analysis of this gene network, we identified the transcriptional factor as a key regulator governing chondrosarcoma progression. We unraveled the functional roles of the identified factor in promoting tumor growth and metastasis of chondrosarcomas in the context of their unique microenvironments.Results:By conducting system-level upstream analysis, we identified a factor as a transcriptional regulator that governs the malignancy gene module. The identified factor was upregulated in chondrosarcoma biopsies associated with a high histological grade and conferred chondrosarcoma cells invasiveness and tumor-initiating capacity. In an orthotopic xenograft mouse model, the identified factor modulated local outgrowth and pulmonary metastasis of chondrosarcoma. Pharmacological inhibition of the identified factor in conjunction with the chemotherapy agents such as cisplatin or doxorubicin synergistically enhanced chondrosarcoma cell apoptosis and abolished malignant phenotypes of chondrosarcoma in mice.Conclusion:Our study provides a proof of concept evidence that inhibiting the identified factor suppresses progression of chondrosarcoma and improves the efficacy of chemotherapy in cellular and pre-clinical levels. Taken together, we believe that our findings provide novel molecular insights for the development of new anti-cancer therapies to target chondrosarcomas.References:[1]Gelderblom H, et al. The clinical approach towards chondrosarcoma. Oncologist 13, 320-329 (2008)Disclosure of Interests:None declared

scholarly journals Autophagy as a mechanism for anti-angiogenic therapy resistance

2020 ◽  
Vol 66 ◽  
pp. 75-88 ◽  
Author(s):  
Ankush Chandra ◽  
Jonathan Rick ◽  
Garima Yagnik ◽  
Manish K. Aghi
Keyword(s):  
Therapy Resistance ◽  
Angiogenic Therapy

Extracellular vesicle-associated proteins as potential biomarkers

2020 ◽  
pp. 1-48
Author(s):  
Anne Sophie Schou ◽  
Jonas Ellegaard Nielsen ◽  
Anders Askeland ◽  
Malene Møller Jørgensen
Keyword(s):  
Extracellular Vesicle ◽  
Associated Proteins ◽  
Potential Biomarkers

scholarly journals Biomarkers in Tumor Angiogenesis and Anti-Angiogenic Therapy

2011 ◽  
Vol 12 (10) ◽  
pp. 7077-7099 ◽  
Author(s):  
Andreas Pircher ◽  
Wolfgang Hilbe ◽  
Isabel Heidegger ◽  
Joachim Drevs ◽  
André Tichelli ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Angiogenic Therapy

Regulation of TRPV5 and TRPV6 by associated proteins

2006 ◽  
Vol 290 (6) ◽  
pp. F1295-F1302 ◽  
Author(s):  
Stan F. J. van de Graaf ◽  
Joost G. J. Hoenderop ◽  
René J. M. Bindels
Keyword(s):  
Molecular Mechanisms ◽  
Hormonal Control ◽  
Trp Channel ◽  
Intestinal Lumen ◽  
Blood Compartment ◽  
Associated Proteins ◽  
The Relationship ◽  
Insight Into ◽  
Prime Target

The epithelial Ca2+ channels TRPV5 and TRPV6 are the most Ca2+-selective members of the TRP channel superfamily. These channels are the prime target for hormonal control of the active Ca2+ flux from the urine space or intestinal lumen to the blood compartment. Insight into their regulation is, therefore, pivotal in our understanding of the (patho)physiology of Ca2+ homeostasis. The recent elucidation of TRPV5/6-associated proteins has provided new insight into the molecular mechanisms underlying the regulation of these channels. In this review, we describe the various means of TRPV5/6 regulation, the role of channel-associated proteins herein, and the relationship between both processes.

Strategies to Suppress Tumor Angiogenesis and Metastasis, Overcome Multi-Drug Resistance in Cancer, Target Telomerase and Apoptosis Pathways

2021 ◽  
pp. 312-338
Author(s):  
Mohd Aleem ◽  
Deepti Sharma ◽  
Deepshikha Sharma ◽  
Siddhartha Dan ◽  
Pooja Gupta ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Cell Cycle Control ◽  
Acquired Resistance ◽  
Multi Drug Resistance ◽  
Signal Transduction Pathways ◽  
Long Time ◽  
Apoptosis Pathways ◽  
Tumor Growth And Metastasis ◽  
Resistance To Chemotherapy

Cancer has been a worldwide topic in the medical field for a very long time. As angiogenesis is essential for tumor growth and metastasis, controlling tumor-associated angiogenesis is a promising tactic in limiting cancer progression. In cancer patients, multidrug resistance (MDR) is most widely used phenomenon by which cancer acquired resistance to chemotherapy. This resistance to chemotherapy occurs due to the formation of insulated tumor microenvironment which remains a major hurdle in the cure of various types of cancer. The mechanisms that cause malignant growth of cells include cell cycle control, signal transduction pathways, apoptosis, telomere stability, and interaction with the extracellular matrix. This chapter focuses on current strategies to suppress tumor angiogenesis for cancer therapy, various mechanisms involved in the development of MDR in cancer cells, which in turn will help us to identify possible strategies to overcome these MDR mechanisms and a variety of procedures that involves targeting apoptotic and telomerase pathways to suppress tumor progression.

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