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Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth
Vrije Univ Amsterdam, Dept Med Oncol, Angiogenesis Lab, Med Ctr, De Boelelaan 1118, NL-1081 HV Amsterdam, Netherlands;Vrije Univ Amsterdam, Dept Radiat Oncol, Med Ctr, Amsterdam, Netherlands.
Vrije Univ Amsterdam, Dept Med Oncol, Angiogenesis Lab, Med Ctr, De Boelelaan 1118, NL-1081 HV Amsterdam, Netherlands;Maastricht Univ, GROW Sch Oncol & Dev Biol, Div Med Oncol, Med Ctr, Maastricht, Netherlands.
Vrije Univ Amsterdam, Dept Med Oncol, Angiogenesis Lab, Med Ctr, De Boelelaan 1118, NL-1081 HV Amsterdam, Netherlands;Univ Geneva, Sch Pharmaceut Sci, Geneva, Switzerland.ORCID iD: 0000-0002-8299-0444
Vrije Univ Amsterdam, Dept Med Oncol, Angiogenesis Lab, Med Ctr, De Boelelaan 1118, NL-1081 HV Amsterdam, Netherlands.
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2018 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 246, no 4, p. 447-458Article in journal (Refereed) Published
Abstract [en]

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. (c) 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Place, publisher, year, edition, pages
2018. Vol. 246, no 4, p. 447-458
Keywords [en]
tumor angiogenesis, imatinib, endothelial cells, melanoma, Ewing sarcoma, perivascular cells, vasculogenic mimicry, vessel stabilization, cancer
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-371040DOI: 10.1002/path.5152ISI: 000450360400008PubMedID: 30101525OAI: oai:DiVA.org:uu-371040DiVA, id: diva2:1275540
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved

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Heldin, Carl-Henrik

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