Comparison of biological phenotypes according to midkine expression in gastric cancer cells and their autocrine activities could be modulated by pentosan polysulfate.
We studied biological phenotypes of gastric cancer cell lines based on a novel heparin-binding growth/differentiation factor (midkine (MK)) expression. MK expression was found in 67% (6/9) of the gastric cancer cell lines and 56% (14/25) of the primary cancer tissues. Gastric cancer cell lines with MK expression showed higher colony forming activity in soft agar assay and endothelial cell growth stimulatory effect in cross-feeding assay than cells which did not express MK. However, urokinase-type plasminogen activator (uPA) expression and tumor invasiveness did not correlate with MK expression. Growth of MK expressing cells was inhibited by a heparin-binding blocking agent, pentosan polysulfate (PPS). In cancer tissues, MK expression correlated with tumor size, suggesting in vivo autocrine and paracrine activity. This proliferation promoting activity of MK can be targeted by an anti-heparin binding agent as a biotherapy model in gastric cancer.
Rha
S Y
SY
Yonsei Cancer Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Noh
S H
SH
Kwak
H J
HJ
Wellstein
A
A
Kim
J H
JH
Roh
J K
JK
Min
J S
JS
Kim
B S
BS
Chung
H C
HC
D001202:Ascitic Fluid; D002352:Carrier Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis; D000078792:Midkine; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D002352:Carrier Proteins; D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000078792:Midkine; D010426:Pentosan Sulfuric Polyester; D014568:Urokinase-Type Plasminogen Activator