TY - JOUR
T1 - Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis
AU - Maussang Detaille, D.A.B.
AU - Verzijl, D.
AU - Stigter-van Walsum, M
AU - Leurs, R.
AU - Holl, J.
AU - Pleskoff, O.C.
AU - Michel, D.
AU - van Dongen, A.A.M.S.
AU - Smit, M.J.
AU - Maussang, David
PY - 2006/8/29
Y1 - 2006/8/29
N2 - Human cytomegalovirus (HCMV) is a widely spread herpesvirus, suggested to play a role in tumor progression. US28, a chemokine receptor encoded by HCMV, binds a broad spectrum of chemokines and constitutively activates various pathways linked to proliferation. Our studies reveal that expression of US28 induces a proangiogenic and transformed phenotype by up-regulating the expression of vascular endothelial growth factor and enhancing cell growth and cell cycle progression. US28-expressing cells promote tumorigenesis when injected into nude mice. The G protein-uncoupled constitutively inactive mutant of US28, induces delayed and attenuated tumor formation, indicating the importance of constitutive receptor activity in the early onset of tumor development. Importantly, also in glioblastoma cells infected with the newly isolated clinical HCMV strain Titan, US28 was shown to be involved in the HCMV-induced angiogenic phenotype. Hence, the constitutively activated chemokine receptor US28 might act as a viral oncogene and enhance and/or promote HCMV-associated tumor progression. © 2006 by The National Academy of Sciences of the USA.
AB - Human cytomegalovirus (HCMV) is a widely spread herpesvirus, suggested to play a role in tumor progression. US28, a chemokine receptor encoded by HCMV, binds a broad spectrum of chemokines and constitutively activates various pathways linked to proliferation. Our studies reveal that expression of US28 induces a proangiogenic and transformed phenotype by up-regulating the expression of vascular endothelial growth factor and enhancing cell growth and cell cycle progression. US28-expressing cells promote tumorigenesis when injected into nude mice. The G protein-uncoupled constitutively inactive mutant of US28, induces delayed and attenuated tumor formation, indicating the importance of constitutive receptor activity in the early onset of tumor development. Importantly, also in glioblastoma cells infected with the newly isolated clinical HCMV strain Titan, US28 was shown to be involved in the HCMV-induced angiogenic phenotype. Hence, the constitutively activated chemokine receptor US28 might act as a viral oncogene and enhance and/or promote HCMV-associated tumor progression. © 2006 by The National Academy of Sciences of the USA.
KW - Cancer
KW - Drug target
KW - G protein-coupled receptor
KW - VEGF
KW - Viral infection
UR - http://www.scopus.com/inward/record.url?scp=33748336259&partnerID=8YFLogxK
U2 - https://doi.org/10.1073/pnas.0604433103
DO - https://doi.org/10.1073/pnas.0604433103
M3 - Article
C2 - 16924106
SN - 0027-8424
VL - 103
SP - 13068
EP - 13073
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IS - 35
ER -