Pivotal Advance: PKCzeta is required for migration of macrophages.

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 (PKCzeta) regulates epidermal growth factor-induced chemotaxis of human breast cancer cells. In this study, we investigated the role of PKCzeta in CSF-1-induced chemotaxis of macrophages. Knockdown of PKCzeta 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 PKCzeta expression also impaired migration of mouse peritoneal macrophages. Scratch analysis indicated that PKCzeta was required for macrophage migration. Therefore, PKCzeta is required for CSF-1-induced chemotaxis of macrophages. Blocking activation of PKCzeta will be a novel strategy to inhibit cancer metastasis by blocking migration of cancer cells and macrophages.

• Authors: Hua Guo, Yongjie Ma, Baogang Zhang, Baocun Sun, Ruifang Niu, Guoguang Ying, Ning Zhang
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 85 Issue 6 Pg. 911-8 (Jun 2009) ISSN: 1938-3673 [Electronic] United States
• PMID: 19201988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Chemokine CCL2
• RNA, Small Interfering
• Macrophage Colony-Stimulating Factor
• protein kinase C zeta
• Protein Kinase C

Topics

• Actins (metabolism)
• Animals
• Cell Line, Tumor
• Cell Movement (drug effects)
• Chemokine CCL2 (pharmacology)
• Chemotaxis (drug effects)
• Down-Regulation (drug effects)
• Gene Knockdown Techniques
• Humans
• Macrophage Colony-Stimulating Factor (pharmacology)
• Macrophages (cytology, drug effects, enzymology)
• Macrophages, Peritoneal (cytology, drug effects, enzymology)
• Mice
• Protein Kinase C (metabolism)
• RNA, Small Interfering (metabolism)