TY - JOUR
T1 - Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth
AU - Thijssen, Victor L. J. L.
AU - Paulis, Yvette W. J.
AU - Nowak-Sliwinska, Patrycja
AU - Deumelandt, Katrin L.
AU - Hosaka, Kayoko
AU - Soetekouw, Patricia M. M. B.
AU - Cimpean, Anca M.
AU - Raica, Marius
AU - Pauwels, Patrick
AU - van den Oord, Joost J.
AU - Tjan-Heijnen, Vivianne C. G.
AU - Hendrix, Mary J.
AU - Heldin, Carl-Henrik
AU - Cao, Yihai
AU - Griffioen, Arjan W.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
KW - tumor angiogenesis
KW - imatinib
KW - endothelial cells
KW - melanoma
KW - Ewing sarcoma
KW - perivascular cells
KW - vasculogenic mimicry
KW - vessel stabilization
KW - cancer
KW - TO-MESENCHYMAL TRANSITION
KW - STEM-LIKE CELLS
KW - PRIMARY CUTANEOUS MELANOMA
KW - ANTI-ANGIOGENIC THERAPY
KW - VASCULOGENIC MIMICRY
KW - ENDOTHELIAL-CELLS
KW - BREAST-CANCER
KW - CO-OPTION
KW - IN-VIVO
KW - METASTASIS
U2 - 10.1002/path.5152
DO - 10.1002/path.5152
M3 - Article
SN - 0022-3417
VL - 246
SP - 447
EP - 458
JO - Journal of Pathology
JF - Journal of Pathology
IS - 4
ER -