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Pericyte-fibroblast Transition Promotes Tumor Growth and Metastasis

Pericyte-fibroblast Transition Promotes Tumor Growth and Metastasis

Kayoko Hosaka, Yunlong Yang, Takahiro Seki, Carina Fischer, Olivier Dubey, Erik Fredlund, Johan Hartman, Piotr Religa, Hiromasa Morikawa, Yoko Ishii, Masakiyo Sasahara, Ola Larsson, Giulio Cossu, Renhai Cao, etc.

Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):E5618-27.

PMID: 27608497

Abstract:

Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte-fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that PDGF-BB-PDGFRβ signaling promotes PFT both in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, TN-AP-CreERT2:R26R-tdTomato and NG2-CreERT2:R26R-tdTomato, shows that PFT cells gain stromal fibroblast and myofibroblast markers in tumors. Importantly, coimplantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells and metastasis. Our findings reveal a mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT, and thus targeting PFT may offer a new treatment option of cancer metastasis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413775	PDGF-BB from mouse			Price

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