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

Nat Commun. 2016 May 6;7:11385. doi: 10.1038/ncomms11385

Speaker: Yi-Zhen Wu (吳宜臻)                            Time: 14:00~15:00, Oct, 12 2016

Commentator: Dr. Bei-Chang Yang (楊倍昌)      Place: Room 601

Abstract:

        Metastasis is the leading reason for the resultant mortality of patients with cancer. Cancer cells often manipulate host cells in the local microenvironment to facilitate their invasion, dissemination and metastasis through signaling molecule. In previous studies showed that the PDGF-PDGFR signaling member PDGF-BB modulates vascular remodelling and maturation by recruiting pericytes and vascular smooth muscle cells onto angiogenic vessels. However, how these perivascular cells been activated in the tumour microenvironment for cancer invasion and metastasis is poorly understood. As we know, tumor-associated macrophages (TAMs) are a major component of infiltrated immune cells in tumor microenvironment and TAMs can promote tumor growth and metastasis. Hence, authors wanted to investigate whether PDGF-BB signaling recruits TAMs to promote cancer metastasis. Authors found that PDGF-BB-expressing tumors contained a high number of TAMs that lacked PDGFR expression. They noticed that IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes by genome-wide expression microarray. A recent study has showed that injection of IL-33 protein stimulates primary tumour growth and metastasis in a mouse breast cancer model. Furthermore, authors utilized gain-of-fuction and loss-of-function experiments to demonstrate that pericyte- and stromal cell-derived IL-33 is a key of cytokine for recruitment of TAMs in the tumor microenvironment. These findings not only define a new pathway of host cell in the tumor microenvironment that controls cancer metastasis, but also demonstrate that TAMs are the primary cell type to leading the metastasis process. Taken together, functional blocking of the PDGF-BB-IL-33-TAM axis is a novel therapeutic option for the treatment of cancer and metastasis.

References:

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