Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature communications, 2016-05, Vol.7 (1), p.11385-11385, Article 11385

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.