Tumour angiogenesis

  • Article
    | Open Access

    UNC5B is a Netrin-1 receptor expressed in endothelial cells that in the absence of ligand induces apoptosis. Here the authors identify an UNC5B splicing isoform that is insensitive to the pro-survival ligand Netrin-1 and is required for apoptosis-dependent blood vessel development.

    • Davide Pradella
    • , Gianluca Deflorian
    •  & Claudia Ghigna
  • Article
    | Open Access

    How STING agonists exert anti-tumour effects remains unclear. Here, the authors show that STING agonists suppress tumor growth of subcutaneous xenografts models inducing early apoptosis of endothelial cells through the TNFalpha-TNFR1 signaling, while in primary tumors, additional inhibition of AKT is required for efficient induction of apoptosis via the same pathway.

    • Seung-hwan Jeong
    • , Myung Jin Yang
    •  & Gou Young Koh
  • Article
    | Open Access

    Cancer associated fibroblasts (CAFs) have been suggested to regulate cancer cell metabolism, but the mechanisms are not completely elucidated. Here, the authors show that low FAK expression in stromal cells correlates with poor prognosis in breast and pancreatic cancer patients and that FAK-silencing in CAFs promotes tumourigenesis by the paracrine regulation of cancer cell metabolism.

    • Fevzi Demircioglu
    • , Jun Wang
    •  & Kairbaan Hodivala-Dilke
  • Article
    | Open Access

    Tumors can overproduce pro-angiogenic ligands overcoming currently approved anti-angiogenic therapies and hindering their success. Here, the authors show that targeting phosphoinositide recycling during tumor angiogenesis harnesses the tumor’s own production of angiogenic ligands to deplete adjacent endothelial cells of the capacity to respond to these signals.

    • Amber N. Stratman
    • , Olivia M. Farrelly
    •  & Brant M. Weinstein
  • Article
    | Open Access

    Mesenchymal cells contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. Here, the authors show that mesenchymal stem cells also have the ability to acquire an endothelial phenotype upon TGF-β stimulation via the downstream kinase JNK, and that p38α negatively regulates this process.

    • Raquel Batlle
    • , Eva Andrés
    •  & Angel R. Nebreda
  • Article
    | Open Access

    Bladder cancer is one of the most common and highly vascularized cancers. Here the authors perform a whole-genome analysis in urothelial bladder carcinomas and identify recurrent genetic alterations in a set of angiogenesis genes, facilitating the understanding of molecular mechanisms underlying pathological angiogenesis in this type of cancer.

    • Song Wu
    • , Tong Ou
    •  & Zhiming Cai
  • Article
    | Open Access

    Measuring multiple neurophysiologic variables usually requires bulky benchtop optical systems and working with anesthetized animals. Here the authors present a miniature portable microscope for neurovascular imaging in awake rodents, combining fluorescence, intrinsic optical signals and laser speckle contrast.

    • Janaka Senarathna
    • , Hang Yu
    •  & Arvind P. Pathak
  • Article
    | Open Access

    EBV latent infection contributes to the pathogenesis of epithelial malignancies by inducing angiogenesis. Here, the authors show EBV promotes vasculogenic mimicry in EBV associated epithelial cancers via AKT/HIF-1α pathway and combination therapy of HIF-1α and VEGF reduces tumour growth.

    • Tong Xiang
    • , Yu-Xin Lin
    •  & Lin Feng
  • Article
    | Open Access

    Identification of response biomarkers is a key step towards the development of personalised care. Here, Jayson et al. identify plasma Tie2 as a biomarker for the response of the tumor vasculature to anti-angiogenics in patients with metastatic colorectal cancer, suggesting that monitoring Tie2 levels may help guide therapy in the clinics.

    • Gordon C. Jayson
    • , Cong Zhou
    •  & Caroline Dive
  • Article
    | Open Access

    Increased copy number alterations, indicative of chromosomal instability, is associated with poor cancer outcome. Here, metastatic colorectal cancer patients displaying intermediate-high CIN associate with improved outcome following chemotherapy and bevacizumab treatment, suggesting CIN as a predictive biomarker.

    • Dominiek Smeets
    • , Ian S. Miller
    •  & Annette T. Byrne
  • Article
    | Open Access

    A soluble form E-cadherin is highly expressed in ovarian cancer. Here, the authors show that soluble E-cadherin is released by ovarian cancer cells packaged in exosomes and promotes tumor angiogenesis through β-catenin and NFkB signaling activation.

    • Maggie K. S. Tang
    • , Patrick Y. K. Yue
    •  & Alice S. T. Wong
  • Article
    | Open Access

    Extracellular matrix plays a central role in driving cancer development. Here the authors using an in vitro approach show that confining collagen architectures induce fast and persistent cell migration and the formation of multicellular network structures linked to vascular mimicry observed in tumours from patients.

    • D. O. Velez
    • , B. Tsui
    •  & S. I. Fraley
  • Article
    | Open Access

    Tumour hypoxia influences both the immune responses and angiogenesis. Here, the authors show that HIF-1α deletion in NK cells impairs NK cytotoxic activity but inhibit tumour growth by decreasing the infiltration of NK cells that express angiostatic soluble VEGFR-1, thus resulting in non-functional angiogenesis.

    • Ewelina Krzywinska
    • , Chahrazade Kantari-Mimoun
    •  & Christian Stockmann
  • Article
    | Open Access

    The incidence of renal cell carcinoma is higher in males than in females due to the different androgen receptor signaling but the molecular mechanisms behind this gender bias are unclear. Here the authors show how androgen receptor expression influences the metastatic route through the regulation of miR-185 and VEGF isoforms.

    • Qingbo Huang
    • , Yin Sun
    •  & Chawnshang Chang
  • Article
    | Open Access

    Angiogenesis is essential for solid tumor progression. Here, the authors interrogate the proteome of pancreatic cancer endothelium via phage display and identify hornerin as a critical protein whose expression is essential to maintain the pancreatic cancer vasculature through a VEGF-independent mechanism.

    • Michael F. Gutknecht
    • , Marc E. Seaman
    •  & Kimberly A. Kelly
  • Article
    | Open Access

    Resistance towards VEGF-centered anti-angiogenic therapy is an important clinical challenge. Here, the authors show that mast cells mediate resistance to anti-angiogenetic inhibitors by altering the proliferative and organizational state of endothelial cells through mobilization of FGF-1 and GM-CSF from the tumor matrix and secretion of FGF-2.

    • M. Wroblewski
    • , R. Bauer
    •  & S. Loges
  • Article
    | Open Access

    The angiopoietins regulate vascular maturation, angiogenesis and lymphangiogenesis via their Tie receptors that were long believed to be endothelium-specific. Here the authors show that angiopoietins activate and control pericyte function through pericyte-expressed Tie2 triggering of Calpain, Akt and FOXO3A signalling cascades.

    • Martin Teichert
    • , Laura Milde
    •  & Hellmut G. Augustin
  • Article
    | Open Access

    Notch signalling is deregulated in several cancers; therefore, strategies targeting this pathway are currently being explored. Here the authors report a pro-apoptotic function of Notch3 in endothelial cells; consequently, when Notch3 is silenced in stroma cells, tumour growth and angiogenesis are increased.

    • Shuheng Lin
    • , Ana Negulescu
    •  & Patrick Mehlen
  • Article
    | Open Access

    Cancer cells can affect cancer progression by producing systemic effects. Here, the authors show that IGF2 produced by oesophageal cancer cells increases secretion of VEGF from cancer-associated fibroblasts resulting in systemic mobilization of bone marrow-derived cells and increased metastases.

    • Wen Wen Xu
    • , Bin Li
    •  & Annie L. M. Cheung
  • Article
    | Open Access

    The tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here the authors show that radiation induced miR-103 downregulates TREX1 in endothelial cells, decreases angiogenesis and leads to the secretion of proinflammatory mediators that reduce tumour growth.

    • RaeAnna Wilson
    • , Cristina Espinosa-Diez
    •  & Sudarshan Anand
  • Article
    | Open Access

    Chemerin is an adipokine often downregulated in tumours. Here the authors show that chemotherapy induces chemerin production by endothelial cells, leading to cachexia, and that VEGF ablation in myeloid cells prevents cachexia in a chemerin-dependent manner, and improves chemotherapeutic effects.

    • Ralph Klose
    • , Ewelina Krzywinska
    •  & Christian Stockmann
  • Article
    | Open Access

    The formation of blood vessels in tumours, angiogenesis, is a promising target for therapy. Here, the authors show that microRNA192 has anti-angiogenic functions and negatively regulates EGR1 and HOXB9, and that delivery of this microRNA to tumours in vivocan reduce angiogenesis and tumour growth.

    • Sherry Y. Wu
    • , Rajesha Rupaimoole
    •  & Anil K. Sood
  • Article |

    The Wilms’ tumour suppressor Wt1 is highly expressed in vessels and stromal cells of human tumours, but not in adjacent healthy tissue. Here the authors show that Wt1 regulates Pecam-1 and c-kitand that deletion of Wt1 in endothelial, haematopoietic and myeloid suppressor cells leads to tumour regression.

    • Kay-Dietrich Wagner
    • , Julien Cherfils-Vicini
    •  & Nicole Wagner
  • Article |

    Tumours acquire new vasculature through angiogenesis or through alternative pathways including the less understood vasculogenesis mimicry. Here the authors identify a vasculogenic mimicry-competent subpopulation of melanoma cells that expresses the vascular cell adhesion molecule PECAM1, but not VEGFR-2.

    • James M. Dunleavey
    • , Lin Xiao
    •  & Andrew C. Dudley
  • Article |

    Tumour angiogenesis is critical for tumour growth and metastasis but the mechanisms that promote the growth of new blood vessels by tumours are not completely clear. Here the authors show that overexpression of the transcription factor Twist1 in certain tumour cells can lead them to differentiate into endothelial cells.

    • Hsiao-Fan Chen
    • , Chi-Hung Huang
    •  & Kou-Juey Wu
  • Article |

    The microRNA-200 family members have a role in regulating tumour angiogenesis but the underlying mechanism is unclear. In this study, Pecot et al.demonstrate that miR-200 affects angiogenesis by altering endothelial and cancer cell cytokine secretion.

    • Chad V. Pecot
    • , Rajesha Rupaimoole
    •  & Anil K. Sood
  • Article |

    Focal adhesion kinase (FAK) regulates angiogenesis and FAK inhibitors are currently developed as anticancer drugs. Here Kostourou and colleagues show that genetic FAK heterozygosity or low doses of a pharmacological FAK inhibitor unexpectedly increase angiogenesis and tumour growth in vitro and in vivo.

    • Vassiliki Kostourou
    • , Tanguy Lechertier
    •  & Kairbaan Hodivala-Dilke