Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth.

Autor: Thijssen VL; Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.; Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands., Paulis YW; Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.; Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands., Nowak-Sliwinska P; Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland., Deumelandt KL; Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands., Hosaka K; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden., Soetekouw PM; Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands., Cimpean AM; Department of Microscopic Morphology, Histology, Angiogenesis Research Center, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania., Raica M; Department of Microscopic Morphology, Histology, Angiogenesis Research Center, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania., Pauwels P; Department of Pathology, Antwerp University Hospital, Edegem, Belgium., van den Oord JJ; Laboratory of Translational Cell and Tissue Research, University of Leuven, Leuven, Belgium., Tjan-Heijnen VC; Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands., Hendrix MJ; Department of Biology, Shepherd University, Shepherdstown University, WV, USA., Heldin CH; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Cao Y; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden., Griffioen AW; Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2018 Dec; Vol. 246 (4), pp. 447-458. Date of Electronic Publication: 2018 Oct 30.
DOI: 10.1002/path.5152
Abstrakt: Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry-positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular-like networks. The pericyte recruitment is mediated through platelet-derived growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular-like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry-positive cancer types. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
(© 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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