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

Sen Chen, Guojun D Bu, Yoshifumi Takei, Kazuma Sakamoto, Shinya Ikematsu, Takashi Muramatsu, Kenji Kadomatsu

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4009-4015
Number of pages7
JournalJournal of Cell Science
Volume120
Issue number22
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-1
Growth
Neoplasms
midkine
midkine receptors
Nude Mice
Fibroblast Growth Factor 2
Conditioned Culture Medium

Keywords

  • Dominant negative
  • LRP1
  • Midkine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells. / Chen, Sen; Bu, Guojun D; Takei, Yoshifumi; Sakamoto, Kazuma; Ikematsu, Shinya; Muramatsu, Takashi; Kadomatsu, Kenji.

In: Journal of Cell Science, Vol. 120, No. 22, 15.11.2007, p. 4009-4015.

Research output: Contribution to journalArticle

Chen, S, Bu, GD, Takei, Y, Sakamoto, K, Ikematsu, S, Muramatsu, T & Kadomatsu, K 2007, 'Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells', Journal of Cell Science, vol. 120, no. 22, pp. 4009-4015. https://doi.org/10.1242/jcs.013946
Chen, Sen ; Bu, Guojun D ; Takei, Yoshifumi ; Sakamoto, Kazuma ; Ikematsu, Shinya ; Muramatsu, Takashi ; Kadomatsu, Kenji. / Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells. In: Journal of Cell Science. 2007 ; Vol. 120, No. 22. pp. 4009-4015.
@article{73dd476ebd6c462b9c994dfc10c6575d,
title = "Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells",
abstract = "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.",
keywords = "Dominant negative, LRP1, Midkine",
author = "Sen Chen and Bu, {Guojun D} and Yoshifumi Takei and Kazuma Sakamoto and Shinya Ikematsu and Takashi Muramatsu and Kenji Kadomatsu",
year = "2007",
month = "11",
day = "15",
doi = "10.1242/jcs.013946",
language = "English (US)",
volume = "120",
pages = "4009--4015",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "22",

}

TY - JOUR

T1 - Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells

AU - Chen, Sen

AU - Bu, Guojun D

AU - Takei, Yoshifumi

AU - Sakamoto, Kazuma

AU - Ikematsu, Shinya

AU - Muramatsu, Takashi

AU - Kadomatsu, Kenji

PY - 2007/11/15

Y1 - 2007/11/15

N2 - 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.

AB - 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.

KW - Dominant negative

KW - LRP1

KW - Midkine

UR - http://www.scopus.com/inward/record.url?scp=37249028744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37249028744&partnerID=8YFLogxK

U2 - 10.1242/jcs.013946

DO - 10.1242/jcs.013946

M3 - Article

C2 - 17971413

AN - SCOPUS:37249028744

VL - 120

SP - 4009

EP - 4015

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 22

ER -