The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth. / Heukers, Raimond; Fan, Tian Shu; de Wit, Raymond H; van Senten, Jeffrey R; De Groof, Timo W M; Bebelman, Maarten P; Lagerweij, Tonny; Vieira, Joao; de Munnik, Sabrina M; Smits-de Vries, Laura; van Offenbeek, Jody; Rahbar, Afsar; van Hoorick, Diane; Söderberg-Naucler, Cecilia; Würdinger, Thomas; Leurs, Rob; Siderius, Marco; Vischer, Henry F; Smit, Martine J.

In: Oncogene, Vol. 37, No. 30, 07.2018, p. 4110-4121.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Heukers, R, Fan, TS, de Wit, RH, van Senten, JR, De Groof, TWM, Bebelman, MP, Lagerweij, T, Vieira, J, de Munnik, SM, Smits-de Vries, L, van Offenbeek, J, Rahbar, A, van Hoorick, D, Söderberg-Naucler, C, Würdinger, T, Leurs, R, Siderius, M, Vischer, HF & Smit, MJ 2018, 'The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth', Oncogene, vol. 37, no. 30, pp. 4110-4121. https://doi.org/10.1038/s41388-018-0255-7

APA

Heukers, R., Fan, T. S., de Wit, R. H., van Senten, J. R., De Groof, T. W. M., Bebelman, M. P., Lagerweij, T., Vieira, J., de Munnik, S. M., Smits-de Vries, L., van Offenbeek, J., Rahbar, A., van Hoorick, D., Söderberg-Naucler, C., Würdinger, T., Leurs, R., Siderius, M., Vischer, H. F., & Smit, M. J. (2018). The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth. Oncogene, 37(30), 4110-4121. https://doi.org/10.1038/s41388-018-0255-7

Vancouver

Heukers R, Fan TS, de Wit RH, van Senten JR, De Groof TWM, Bebelman MP et al. The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth. Oncogene. 2018 Jul;37(30):4110-4121. https://doi.org/10.1038/s41388-018-0255-7

Author

Heukers, Raimond ; Fan, Tian Shu ; de Wit, Raymond H ; van Senten, Jeffrey R ; De Groof, Timo W M ; Bebelman, Maarten P ; Lagerweij, Tonny ; Vieira, Joao ; de Munnik, Sabrina M ; Smits-de Vries, Laura ; van Offenbeek, Jody ; Rahbar, Afsar ; van Hoorick, Diane ; Söderberg-Naucler, Cecilia ; Würdinger, Thomas ; Leurs, Rob ; Siderius, Marco ; Vischer, Henry F ; Smit, Martine J. / The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth. In: Oncogene. 2018 ; Vol. 37, No. 30. pp. 4110-4121.

Bibtex

@article{8952160c1d464b169fc3c4408ec44f14,
title = "The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth",
abstract = "Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA and encoded proteins, including the chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity and is able to bind several human chemokines, leading to the activation of various proliferative and inflammatory signaling pathways. Here we show that HCMV, through the expression of US28, significantly enhanced the growth of 3D spheroids of U251- and neurospheres of primary glioblastoma cells. Moreover, US28 expression accelerated the growth of glioblastoma cells in an orthotopic intracranial GBM-model in mice. We developed highly potent and selective US28-targeting nanobodies, which bind to the extracellular domain of US28 and detect US28 in GBM tissue. The nanobodies inhibited chemokine binding and reduced the constitutive US28-mediated signaling with nanomolar potencies and significantly impaired HCMV/US28-mediated tumor growth in vitro and in vivo. This study emphasizes the oncomodulatory role of HCMV-encoded US28 and provides a potential therapeutic approach for HCMV-positive tumors using the nanobody technology.",
keywords = "Animals, Brain Neoplasms/genetics, COS Cells, Cell Line, Cell Proliferation/genetics, Cercopithecus aethiops, Cytomegalovirus/genetics, Female, Glioblastoma/genetics, HEK293 Cells, Humans, Mice, Mice, Nude, NIH 3T3 Cells, Receptors, Chemokine/genetics, Receptors, Virus/genetics, Signal Transduction/genetics, Viral Proteins/genetics",
author = "Raimond Heukers and Fan, {Tian Shu} and {de Wit}, {Raymond H} and {van Senten}, {Jeffrey R} and {De Groof}, {Timo W M} and Bebelman, {Maarten P} and Tonny Lagerweij and Joao Vieira and {de Munnik}, {Sabrina M} and {Smits-de Vries}, Laura and {van Offenbeek}, Jody and Afsar Rahbar and {van Hoorick}, Diane and Cecilia S{\"o}derberg-Naucler and Thomas W{\"u}rdinger and Rob Leurs and Marco Siderius and Vischer, {Henry F} and Smit, {Martine J}",
year = "2018",
month = jul,
doi = "10.1038/s41388-018-0255-7",
language = "English",
volume = "37",
pages = "4110--4121",
journal = "Oncogene",
issn = "0950-9232",
publisher = "nature publishing group",
number = "30",

}

RIS

TY - JOUR

T1 - The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth

AU - Heukers, Raimond

AU - Fan, Tian Shu

AU - de Wit, Raymond H

AU - van Senten, Jeffrey R

AU - De Groof, Timo W M

AU - Bebelman, Maarten P

AU - Lagerweij, Tonny

AU - Vieira, Joao

AU - de Munnik, Sabrina M

AU - Smits-de Vries, Laura

AU - van Offenbeek, Jody

AU - Rahbar, Afsar

AU - van Hoorick, Diane

AU - Söderberg-Naucler, Cecilia

AU - Würdinger, Thomas

AU - Leurs, Rob

AU - Siderius, Marco

AU - Vischer, Henry F

AU - Smit, Martine J

PY - 2018/7

Y1 - 2018/7

N2 - Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA and encoded proteins, including the chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity and is able to bind several human chemokines, leading to the activation of various proliferative and inflammatory signaling pathways. Here we show that HCMV, through the expression of US28, significantly enhanced the growth of 3D spheroids of U251- and neurospheres of primary glioblastoma cells. Moreover, US28 expression accelerated the growth of glioblastoma cells in an orthotopic intracranial GBM-model in mice. We developed highly potent and selective US28-targeting nanobodies, which bind to the extracellular domain of US28 and detect US28 in GBM tissue. The nanobodies inhibited chemokine binding and reduced the constitutive US28-mediated signaling with nanomolar potencies and significantly impaired HCMV/US28-mediated tumor growth in vitro and in vivo. This study emphasizes the oncomodulatory role of HCMV-encoded US28 and provides a potential therapeutic approach for HCMV-positive tumors using the nanobody technology.

AB - Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA and encoded proteins, including the chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity and is able to bind several human chemokines, leading to the activation of various proliferative and inflammatory signaling pathways. Here we show that HCMV, through the expression of US28, significantly enhanced the growth of 3D spheroids of U251- and neurospheres of primary glioblastoma cells. Moreover, US28 expression accelerated the growth of glioblastoma cells in an orthotopic intracranial GBM-model in mice. We developed highly potent and selective US28-targeting nanobodies, which bind to the extracellular domain of US28 and detect US28 in GBM tissue. The nanobodies inhibited chemokine binding and reduced the constitutive US28-mediated signaling with nanomolar potencies and significantly impaired HCMV/US28-mediated tumor growth in vitro and in vivo. This study emphasizes the oncomodulatory role of HCMV-encoded US28 and provides a potential therapeutic approach for HCMV-positive tumors using the nanobody technology.

KW - Animals

KW - Brain Neoplasms/genetics

KW - COS Cells

KW - Cell Line

KW - Cell Proliferation/genetics

KW - Cercopithecus aethiops

KW - Cytomegalovirus/genetics

KW - Female

KW - Glioblastoma/genetics

KW - HEK293 Cells

KW - Humans

KW - Mice

KW - Mice, Nude

KW - NIH 3T3 Cells

KW - Receptors, Chemokine/genetics

KW - Receptors, Virus/genetics

KW - Signal Transduction/genetics

KW - Viral Proteins/genetics

U2 - 10.1038/s41388-018-0255-7

DO - 10.1038/s41388-018-0255-7

M3 - Journal article

C2 - 29706656

VL - 37

SP - 4110

EP - 4121

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 30

ER -

ID: 217942699