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

Victor L. J. L. Thijssen, Yvette W. J. Paulis, Patrycja Nowak-Sliwinska, Katrin L. Deumelandt, Kayoko Hosaka, Patricia M. M. B. Soetekouw, Anca M. Cimpean, Marius Raica, Patrick Pauwels, Joost J. van den Oord, Vivianne C. G. Tjan-Heijnen, Mary J. Hendrix, Carl-Henrik Heldin, Yihai Cao, Arjan W. Griffioen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)447-458
JournalJournal of Pathology
Volume246
Issue number4
DOIs
Publication statusPublished - 2018

Cite this

Thijssen, V. L. J. L., Paulis, Y. W. J., Nowak-Sliwinska, P., Deumelandt, K. L., Hosaka, K., Soetekouw, P. M. M. B., ... Griffioen, A. W. (2018). Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth. Journal of Pathology, 246(4), 447-458. https://doi.org/10.1002/path.5152