Heparanase augments inflammatory chemokine production from colorectal carcinoma cell lines.
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| Abstract |
To explore possible roles of heparanase in cancer-host crosstalk, we examined whether heparanase influences expression of inflammatory chemokines in colorectal cancer cells. Murine colorectal carcinoma cells incubated with heparanase upregulated MCP-1, KC, and RANTES genes and released MCP-1 and KC proteins. Heparanase-dependent production of IL-8 was detected in two human colorectal carcinoma cell lines. Addition of a heparanase inhibitor Heparastatin (SF4) did not influence MCP-1 production, while both latent and mature forms of heparanase augmented MCP-1 release, suggesting that heparanase catalytic activity was dispensable for MCP-1 production. In contrast, addition of heparin to the medium suppressed MCP-1 release in a dose-dependent manner. Similarly, targeted suppression of Ext1 by RNAi significantly suppressed cell surface expression of heparan sulfate and MCP-1 production in colon 26 cells. Taken together, it is concluded that colon 26 cells transduce the heparanase-mediated signal through heparan sulfate binding. We propose a novel function for heparanase independent of its endoglycosidase activity, namely as a stimulant for chemokine production.
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| Authors | Naoki Tsunekawa, Nobuaki Higashi, Yusuke Kogane, Michihiko Waki, Hiroaki Shida, Yoshio Nishimura, Hayamitsu Adachi, Motowo Nakajima, Tatsuro Irimura |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 469 Issue 4 Pg. 878-83 (Jan 22 2016) ISSN: 1090-2104 [Electronic] United States |
| PMID | 26713365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
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