spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 30 October 2007
doi: 10.1242/jcs.013946

Journal of Cell Science 120, 4009-4015 (2007)
Published by The Company of Biologists 2007
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.013946v1
120/22/4009    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, S.
Right arrow Articles by Kadomatsu, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, S.
Right arrow Articles by Kadomatsu, K.

Research Article

Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells

Sen Chen1, Guojun Bu2,3, Yoshifumi Takei1, Kazuma Sakamoto1, Shinya Ikematsu4, Takashi Muramatsu5 and Kenji Kadomatsu1,*

1 Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
2 Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA
3 Department of Cell Biology and Physiology, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA
4 Department of Bioresources Engineering, Okinawa National College of Technology, Okinawa 905-2192, Japan
5 Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi 470-0195, Japan

* Author for correspondence (e-mail: kkadoma{at}med.nagoya-u.ac.jp)

Accepted 4 September 2007

The growth factor midkine (MK) is highly associated with cancer progression. Knockdown of MK expression strikingly suppresses tumor growth in nude mice. Thus, MK is a candidate target for cancer treatment. LDL-receptor-related protein 1 (LRP1) is a receptor for MK. We found that among the four ligand-binding domains of LRP1, the N-terminal half of the second domain (designated as MK-TRAP) had the strongest affinity to MK. MK-TRAP bound to MK, but not to HB-GAM/pleiotrophin, basic fibroblast growth factor or platelet-derived growth factor (PDGF)-BB. Exogenous MK-TRAP inhibited the binding between MK and LRP1. G401 cells that transiently or stably overexpress MK-TRAP showed decreased cell growth in monolayer culture and reduced colony formation in soft agar, which could be rescued by exogenous MK administration. MK-TRAP collected from conditioned medium also inhibited anchorage-independent growth of G401 cells and CMT-93 cells. Anti-MK antibody also inhibited the anchorage-independent growth. CMT-93 cells stably expressing MK-TRAP formed smaller tumors in a xenograft nude mouse model than control cells. Moreover, GST-RAP, a potent inhibitor of LRP1, inhibited the anchorage-independent growth of control G401 cells but not that of MK-TRAP stable transformants. Collectively, these data demonstrate a crucial role of MK-LRP1 signaling in anchorage-independent cell growth.

Key words: Midkine, LRP1, Dominant negative






© The Company of Biologists Ltd 2007