Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo.
Matrilysin produced by human colon cancer cells may be involved in the progression and metastasis of cancer. In the present study, we investigated the association of matrilysin with angiogenesis. One microgram of recombinant matrilysin is confirmed to have increased [3H]-thymidine uptake in human umbilical vein endothelial cells. Then we used micro encapsulation and a mouse hemoglobin enzyme-linked immunosorbent assay system for in vivo quantitation of angiogenesis with BALB/c nu/nu athymic mice. Hundred micrograms of recombinant matrilysin induced angiogenesis to the same degree as 10 microg of basic fibroblast growth factor (bFGF). Angiogenesis was observed at the site implanted with human colon cancer WiDr cells in agarose micro beads. This was inhibited by subcutaneous injection of matrilysin-specific antisense oligonucleotide significantly by 53%. In conclusion, matrilysin may be associated with angiogenesis of human colon cancer through the direct proliferative action on endothelial cells.
Nishizuka
I
I
Department of Surgery-2, Yokohama City University, School of Medicine, 3-9 Fukuura Kanazawa-ku, 236-0004, Yokohama, Japan. itaru@gsc.riken.go.jp
Ichikawa
Y
Y
Ishikawa
T
T
Kamiyama
M
M
Hasegawa
S
S
Momiyama
N
N
Miyazaki
K
K
Shimada
H
H
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D020783:Matrix Metalloproteinase 7 / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D012685:Sepharose / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D016895:Culture Media, Serum-Free; D016376:Oligonucleotides, Antisense; D016222:Fibroblast Growth Factor 2; D004247:DNA; D012685:Sepharose; D020783:Matrix Metalloproteinase 7