Matrilysin stimulates DNA synthesis of cultured vascular endothelial cellsand induces angiogenesis in vivo

Matrilysin produced by human colon cancer cells may be involved in the prog ression 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 [H-3]-thymidine uptake in human u mbilical vein endothelial cells. Then we used micro encapsulation and a mou se hemoglobin enzyme-linked immunosorbent assay system for in vivo quantita tion of angiogenesis with BALB/c nu/nu athymic mice. Hundred micrograms of recombinant matrilysin induced angiogenesis to the same degree as 10 mug of basic fibroblast growth factor (bFGF). Angiogenesis was observed at the si te implanted with human colon cancer WiDr cells in agarose micro beads. Thi s was inhibited by subcutaneous injection of matrilysin-specific antisense oligonucleotide significantly by 53%. In conclusion, matrilysin may be asso ciated with angiogenesis of human colon cancer through the direct prolifera tive action on endothelial cells. (C) 2001 Published by Elsevier Science Ir eland Ltd.