The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

Yunlong Yang; Patrik Andersson; Kayoko Hosaka; Yin Zhang; Renhai Cao; Hideki Iwamoto; Xiaojuan Yang; Masaki Nakamura; Jian Wang; Rujie Zhuang; Hiromasa Morikawa; Yuan Xue; Harald Braun; Rudi Beyaert; Nilesh Samani; Susumu Nakae; Emily Hams; Steen Dissing; Padraic G Fallon; Robert Langer; Yihai Cao

doi:10.1038/ncomms11385

The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

Yunlong Yang, Patrik Andersson, Kayoko Hosaka, Yin Zhang, Renhai Cao, Hideki Iwamoto, Xiaojuan Yang, Masaki Nakamura, Jian Wang, Rujie Zhuang, Hiromasa Morikawa, Yuan Xue, Harald Braun, Rudi Beyaert, Nilesh Samani, Susumu Nakae, Emily Hams, Steen Dissing, Padraic G Fallon, Robert LangerYihai Cao

ICMM Section 8

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Abstract

Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.

Original language	English
Journal	Nature Communications
Volume	7
Pages (from-to)	11385
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms11385
Publication status	Published - 6 May 2016

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Yang, Y., Andersson, P., Hosaka, K., Zhang, Y., Cao, R., Iwamoto, H., Yang, X., Nakamura, M., Wang, J., Zhuang, R., Morikawa, H., Xue, Y., Braun, H., Beyaert, R., Samani, N., Nakae, S., Hams, E., Dissing, S., Fallon, P. G., ... Cao, Y. (2016). The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages. Nature Communications, 7, 11385. https://doi.org/10.1038/ncomms11385

Yang, Y, Andersson, P, Hosaka, K, Zhang, Y, Cao, R, Iwamoto, H, Yang, X, Nakamura, M, Wang, J, Zhuang, R, Morikawa, H, Xue, Y, Braun, H, Beyaert, R, Samani, N, Nakae, S, Hams, E, Dissing, S, Fallon, PG, Langer, R & Cao, Y 2016, 'The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages', Nature Communications, vol. 7, pp. 11385. https://doi.org/10.1038/ncomms11385

@article{08ce3e6922314e42b19aed7727ed8b2a,

title = "The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages",

abstract = "Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.",

author = "Yunlong Yang and Patrik Andersson and Kayoko Hosaka and Yin Zhang and Renhai Cao and Hideki Iwamoto and Xiaojuan Yang and Masaki Nakamura and Jian Wang and Rujie Zhuang and Hiromasa Morikawa and Yuan Xue and Harald Braun and Rudi Beyaert and Nilesh Samani and Susumu Nakae and Emily Hams and Steen Dissing and Fallon, {Padraic G} and Robert Langer and Yihai Cao",

year = "2016",

month = may,

day = "6",

doi = "10.1038/ncomms11385",

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T1 - The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

AU - Yang, Yunlong

AU - Andersson, Patrik

AU - Hosaka, Kayoko

AU - Zhang, Yin

AU - Cao, Renhai

AU - Iwamoto, Hideki

AU - Yang, Xiaojuan

AU - Nakamura, Masaki

AU - Wang, Jian

AU - Zhuang, Rujie

AU - Morikawa, Hiromasa

AU - Xue, Yuan

AU - Braun, Harald

AU - Beyaert, Rudi

AU - Samani, Nilesh

AU - Nakae, Susumu

AU - Hams, Emily

AU - Dissing, Steen

AU - Fallon, Padraic G

AU - Langer, Robert

AU - Cao, Yihai

PY - 2016/5/6

Y1 - 2016/5/6

N2 - Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.

AB - Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.

U2 - 10.1038/ncomms11385

DO - 10.1038/ncomms11385

M3 - Journal article

C2 - 27150562

SN - 2041-1723

VL - 7

SP - 11385

JO - Nature Communications

JF - Nature Communications

ER -

The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

Abstract

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