Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis

Sunhwa Kim, Hiroyuki Takahashi, Wan-Wan Lin, Pascal Descargues, Sergei Grivennikov, Youngjun Kim, Jun-Li Luo and Michael Karin ()
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Sunhwa Kim: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Hiroyuki Takahashi: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Wan-Wan Lin: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Pascal Descargues: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Sergei Grivennikov: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Youngjun Kim: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Jun-Li Luo: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Michael Karin: School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA

Nature, 2009, vol. 457, issue 7225, 102-106

Abstract: Versican drives metastasis Distant-site metastases are the leading cause of cancer-associated mortality. A study of the inflammatory microenvironment of cancer cells has identified versican, an extracellular matrix proteoglycan, as a possible factor in driving metastasis. It was isolated from the highly metastatic Lewis lung carcinoma cells as a potent inducer of macrophage activation. Versican, which is upregulated in many human tumours, stimulates bone marrow cells via the Toll-like receptor TLR2 to produce the inflammatory protein TNF-?, which enhances the spread of metastases. This points to versican and the other components of this signalling pathway as potential targets for antimetastatic intervention.

Date: 2009
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DOI: 10.1038/nature07623

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