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Originally published online as doi:10.1189/jlb.0708429 on February 6, 2009

Published online before print February 6, 2009
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(Journal of Leukocyte Biology. 2009;85:911-918.)
© 2009 by Society for Leukocyte Biology

Pivotal Advance: PKC{zeta} is required for migration of macrophages

Hua Guo*,{dagger},1, Yongjie Ma*,1, Baogang Zhang*, Baocun Sun*, Ruifang Niu*, Guoguang Ying* and Ning Zhang*,2

* Tianjin Medical University Cancer Institute and Hospital, Research Center of Basic Medical Sciences, Tianjin, China; and
{dagger} Tianjin Medical College, Tianjin, China

2 Correspondence: Tianjin Medical University, Research Center of Basic Medical Sciences and Cancer Institute and Hospital, Tianjin, 300060, China. E-mail: zhangning{at}tijmu.edu.cn

ABSTRACT

The crosstalk, mediated by chemoattractants, between cancer cells and tumor-associated macrophages, plays an important role in tumor invasion and metastasis. Our previous study reported that atypical protein kinase C {zeta} (PKC{zeta}) regulates epidermal growth factor-induced chemotaxis of human breast cancer cells. In this study, we investigated the role of PKC{zeta} in CSF-1-induced chemotaxis of macrophages. Knockdown of PKC{zeta} by small interference RNA impaired CSF-1-induced chemotaxis of human acute monocytic leukemia cell line THP-1, which was probably a result of a decrease in CSF-1-induced phosphorylation of LIN-11, Is11, and MEC-3 protein domain kinase (LIMK)/cofilin and actin polymerization. Furthermore, silencing PKC{zeta} expression also impaired migration of mouse peritoneal macrophages. Scratch analysis indicated that PKC{zeta} was required for macrophage migration. Therefore, PKC{zeta} is required for CSF-1-induced chemotaxis of macrophages. Blocking activation of PKC{zeta} will be a novel strategy to inhibit cancer metastasis by blocking migration of cancer cells and macrophages.

Key Words: CSF-1 • chemokine • metastasis • tumor-associated macrophages




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