Tumour Angiogenesis

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2013) | Viewed by 58596

Special Issue Editor

Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore
Interests: angiogenesis; cancer microenvironment; anti-angiogenic proteins; endothelial cell biology; hepatogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumor angiogenesis is critical for both tumor progression and metastasis. Hence targeting tumor angiogenesis as a therapeutic anticancer approach has been actively pursued for many years. Despite the initial success in animal tumor models and some degree of effectiveness in prolonging the survival of human cancer patients, limitations of efficacy plus inherent as well as acquired resistance in human cancers still plague this therapeutic approach. Hence, further understanding of the molecular and cellular mechanisms of tumor angiogenesis are essential for the advancement of effective antiangiogenic therapy. This special issue will focus on new advancement in the biology and drug targeting of tumor angiogenesis.

We are looking forward to your contributions.

Dr. Ruowen Ge
Guest Editor

Manuscript Submission Information

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Keywords

  • tumor angiogenesis regulator
  • tumor vasculogenesis
  • signaling pathways
  • antiangiogenic drug resistance
  • pericytes and vessel structure
  • vessel integrity
  • vascular permeability
  • endothelial cell junctions
  • metastasis
  • tumor microenvironment
  • tumor angiogenesis markers

Published Papers (6 papers)

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Research

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741 KiB  
Article
Effects of Ellagic Acid on Angiogenic Factors in Prostate Cancer Cells
by Luca Vanella, Claudia Di Giacomo, Rosaria Acquaviva, Ignazio Barbagallo, Giovanni Li Volti, Venera Cardile, Nader G. Abraham and Valeria Sorrenti
Cancers 2013, 5(2), 726-738; https://doi.org/10.3390/cancers5020726 - 19 Jun 2013
Cited by 75 | Viewed by 9594
Abstract
Background: Several natural antioxidants, including ellagic acid (EA), have been reported to have chemotherapeutic activity in vivo and in vitro settings. Cytochrome P450 (CYP) activity and synthesis of both epoxyeicosatrienoic acids (EETs) and 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), together with vascular endothelial growth factor [...] Read more.
Background: Several natural antioxidants, including ellagic acid (EA), have been reported to have chemotherapeutic activity in vivo and in vitro settings. Cytochrome P450 (CYP) activity and synthesis of both epoxyeicosatrienoic acids (EETs) and 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), together with vascular endothelial growth factor (VEGF) and heme oxygenase system (HO) have emerged as important modulators of tumor growth and metastasis. Methods: The anti-angiogenic effects of EA were investigated in the human prostatic cancer cell line LnCap. HO-1, HO-2, CYP2J2 and soluble epoxyde hydrolase (sEH) expressions were evaluated by western blotting. Levels of VEGF and osteoprotegerin (OPG) were determined in the culture supernatant using an ELISA assay, while CYP mRNAs were determined by qRT-PCR. Results: EA treatment induced a significant decrease (p < 0.05) in HO-1, HO-2 and CYP2J2 expression, and in VEGF and OPG levels. Similarly CYP2J2, CYP4F2 and CYPA22 mRNAs were significantly (p < 0.05) down-regulated by EA treatment. The decrease in CYP2J2 mRNA was associated with an increase in sEH expression. Conclusions: Results reported in the present study highlighted the ability of EA to modulate a new pathway, in addition to anti-proliferative and pro-differentiation properties, via a mechanism that involves a decrease in eicosanoid synthesis and a down-regulation of the HO system in prostate cancer. Full article
(This article belongs to the Special Issue Tumour Angiogenesis)
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Review

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502 KiB  
Review
Critical Role of Aberrant Angiogenesis in the Development of Tumor Hypoxia and Associated Radioresistance
by Gabriele Multhoff, Jürgen Radons and Peter Vaupel
Cancers 2014, 6(2), 813-828; https://doi.org/10.3390/cancers6020813 - 08 Apr 2014
Cited by 43 | Viewed by 9082
Abstract
Newly formed microvessels in most solid tumors show an abnormal morphology and thus do not fulfil the metabolic demands of the growing tumor mass. Due to the chaotic and heterogeneous tumor microcirculation, a hostile tumor microenvironment develops, that is characterized inter alia by [...] Read more.
Newly formed microvessels in most solid tumors show an abnormal morphology and thus do not fulfil the metabolic demands of the growing tumor mass. Due to the chaotic and heterogeneous tumor microcirculation, a hostile tumor microenvironment develops, that is characterized inter alia by local hypoxia, which in turn can stimulate the HIF-system. The latter can lead to tumor progression and may be involved in hypoxia-mediated radioresistance of tumor cells. Herein, cellular and molecular mechanisms in tumor angiogenesis are discussed that, among others, might impact hypoxia-related radioresistance. Full article
(This article belongs to the Special Issue Tumour Angiogenesis)
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663 KiB  
Review
Leptin’s Pro-Angiogenic Signature in Breast Cancer
by Ruben Rene Gonzalez-Perez, Viola Lanier and Gale Newman
Cancers 2013, 5(3), 1140-1162; https://doi.org/10.3390/cancers5031140 - 06 Sep 2013
Cited by 55 | Viewed by 9725
Abstract
Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer play an essential [...] Read more.
Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer play an essential role in the disease. Leptin, the main adipokine secreted by adipose tissue, is also abnormally expressed together with its receptor (OB-R) by breast cancer cells. Leptin induces proliferation and angiogenic differentiation of endothelial cells upregulates VEGF/VEGFR2 and transactivates VEGFR2 independent of VEGF. Leptin induces two angiogenic factors: IL-1 and Notch that can increase VEGF expression. Additionally, leptin induces the secretion and synthesis of proteases and adhesion molecules needed for the development of angiogenesis. Leptin’s paracrine actions can further affect stromal cells and tumor associated macrophages, which express OB-R and secrete VEGF and IL-1, respectively. A complex crosstalk between leptin, Notch and IL-1 (NILCO) that induces VEGF/VEGFR2 is found in breast cancer. Leptin actions in tumor angiogenesis could amplify, be redundant and/or compensatory to VEGF signaling. Current failure of breast cancer anti-angiogenic therapies emphasizes the necessity of targeting the contribution of other pro-angiogenic factors in breast cancer. Leptin’s impact on tumor angiogenesis could be a novel target for breast cancer, especially in obese patients. However, more research is needed to establish the importance of leptin in tumor angiogenesis. This review is focused on updated information on how leptin could contribute to tumor angiogenesis. Full article
(This article belongs to the Special Issue Tumour Angiogenesis)
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634 KiB  
Review
Influence of Levamisole and Other Angiogenesis Inhibitors on Angiogenesis and Endothelial Cell Morphology in Vitro
by Tina Friis, Anne-Marie Engel, Christine D. Bendiksen, Line S. Larsen and Gunnar Houen
Cancers 2013, 5(3), 762-785; https://doi.org/10.3390/cancers5030762 - 24 Jun 2013
Cited by 21 | Viewed by 9013
Abstract
Angiogenesis, the formation of new blood vessels from existing vessels is required for many physiological processes and for growth of solid tumors. Initiated by hypoxia, angiogenesis involves binding of angiogenic factors to endothelial cell (EC) receptors and activation of cellular signaling, differentiation, migration, [...] Read more.
Angiogenesis, the formation of new blood vessels from existing vessels is required for many physiological processes and for growth of solid tumors. Initiated by hypoxia, angiogenesis involves binding of angiogenic factors to endothelial cell (EC) receptors and activation of cellular signaling, differentiation, migration, proliferation, interconnection and canalization of ECs, remodeling of the extracellular matrix and stabilization of newly formed vessels. Experimentally, these processes can be studied by several in vitro and in vivo assays focusing on different steps in the process. In vitro, ECs form networks of capillary-like tubes when propagated for three days in coculture with fibroblasts. The tube formation is dependent on vascular endothelial growth factor (VEGF) and omission of VEGF from the culture medium results in the formation of clusters of undifferentiated ECs. Addition of angiogenesis inhibitors to the coculture system disrupts endothelial network formation and influences EC morphology in two distinct ways. Treatment with antibodies to VEGF, soluble VEGF receptor, the VEGF receptor tyrosine kinase inhibitor SU5614, protein tyrosine phosphatase inhibitor (PTPI) IV or levamisole results in the formation of EC clusters of variable size. This cluster morphology is a result of inhibited EC differentiation and levamisole can be inferred to influence and block VEGF signaling. Treatment with platelet factor 4, thrombospondin, rapamycin, suramin, TNP-470, salubrinal, PTPI I, PTPI II, clodronate, NSC87877 or non-steriodal anti-inflammatory drugs (NSAIDs) results in the formation of short cords of ECs, which suggests that these inhibitors have an influence on later steps in the angiogenic process, such as EC proliferation and migration. A humanized antibody to VEGF is one of a few angiogenesis inhibitors used clinically for treatment of cancer. Levamisole is approved for clinical treatment of cancer and is interesting with respect to anti-angiogenic activity in vivo since it inhibits ECs in vitro with a morphology resembling that obtained with antibodies to VEGF. Full article
(This article belongs to the Special Issue Tumour Angiogenesis)
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Review
Emerging Roles of ADAMTSs in Angiogenesis and Cancer
by Saran Kumar, Nithya Rao and Ruowen Ge
Cancers 2012, 4(4), 1252-1299; https://doi.org/10.3390/cancers4041252 - 29 Nov 2012
Cited by 63 | Viewed by 11915
Abstract
A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs—ADAMTSs—are a multi-domain, secreted, extracellular zinc metalloproteinase family with 19 members in humans. These extracellular metalloproteinases are known to cleave a wide range of substrates in the extracellular matrix. They have been implicated in various physiological processes, [...] Read more.
A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs—ADAMTSs—are a multi-domain, secreted, extracellular zinc metalloproteinase family with 19 members in humans. These extracellular metalloproteinases are known to cleave a wide range of substrates in the extracellular matrix. They have been implicated in various physiological processes, such as extracellular matrix turnover, melanoblast development, interdigital web regression, blood coagulation, ovulation, etc. ADAMTSs are also critical in pathological processes such as arthritis, atherosclerosis, cancer, angiogenesis, wound healing, etc. In the past few years, there has been an explosion of reports concerning the role of ADAMTS family members in angiogenesis and cancer. To date, 10 out of the 19 members have been demonstrated to be involved in regulating angiogenesis and/or cancer. The mechanism involved in their regulation of angiogenesis or cancer differs among different members. Both angiogenesis-dependent and -independent regulation of cancer have been reported. This review summarizes our current understanding on the roles of ADAMTS in angiogenesis and cancer and highlights their implications in cancer therapeutic development. Full article
(This article belongs to the Special Issue Tumour Angiogenesis)
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246 KiB  
Review
A microRNA Link to Glioblastoma Heterogeneity
by Sanjay K. Singh, Alenoush Vartanian, Kelly Burrell and Gelareh Zadeh
Cancers 2012, 4(3), 846-872; https://doi.org/10.3390/cancers4030846 - 03 Sep 2012
Cited by 13 | Viewed by 8646
Abstract
Glioblastomas (GBM) are one of the most malignant adult primary brain tumors. Through decades of research using various model systems and GBM patients, we have gained considerable insights into the mechanisms regulating GBM pathogenesis, but have mostly failed to significantly improve clinical outcome. [...] Read more.
Glioblastomas (GBM) are one of the most malignant adult primary brain tumors. Through decades of research using various model systems and GBM patients, we have gained considerable insights into the mechanisms regulating GBM pathogenesis, but have mostly failed to significantly improve clinical outcome. For the most part GBM heterogeneity is responsible for this lack of progress. Here, we have discussed sources of cellular and microenvironmental heterogeneity in GBMs and their potential regulation through microRNA mediated mechanisms. We have focused on the role of individual microRNAs (miRNA) through their specific targets and miRNA mediated RNA-RNA interaction networks with the potential to influence various aspects of GBM heterogeneity including tumor neo-vascularization. We believe a better understanding of such mechanisms for regulation of GBM pathogenesis will be instrumental for future therapeutic options. Full article
(This article belongs to the Special Issue Tumour Angiogenesis)
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