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MMP-7 (matrilysin) accelerated growth of human umbilical vein endothelial cells
Nailin Huo1, Yasushi Ichikawa, Masako Kamiyama
1Department of Surgery-2, Yokohama City University School of Medicine, 3-9 Fukuura kanazawa-ku, Yokohama 236-0004, Japan.
Abstract:
Matrix metalloproteinases (MMP) are considered to play important roles in angiogenesis. In angiogenic processes, endothelial cells secrete MMP-2 or MMP-1 to dissolve the basement membrane or connective tissue around the vessels. MMP-7 (matrilysin) is secreted from the neovasculars induced by cancer and is a metastatic factor of colorectal cancer. The effect of matrilysin on angiogenesis is still unclear, however. We therefore examined the effect of MMP-7 on the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro. Our results showed that recombinant MMP-7 (rMMP-7) accelerated the proliferation of endothelial cells dose-dependently, and did so for endothelial cells cultured not only on type IV collagen, but also on type I collagen. MMP-7 also upregulated MMP-1, -2 secretion, but did not stimulate vascular endothelial growth factor (VEGF) secretion. From this study, we conclude that MMP-7 directly induces angiogenesis, and that therefore MMP-7 would be a good target of cancer therapy.
Insights
Matrix metalloproteinase-7 (MMP-7) directly promotes angiogenesis by accelerating endothelial cell proliferation. This finding suggests MMP-7 is a potential therapeutic target for cancer treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Matrix metalloproteinases (MMPs) are crucial in angiogenesis.
- MMP-7 (matrilysin) is linked to cancer metastasis, but its role in angiogenesis is unclear.
Purpose of the Study:
- To investigate the effect of MMP-7 on the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro.
- To determine if MMP-7 directly influences angiogenic processes.
Main Methods:
- Recombinant MMP-7 (rMMP-7) was used to treat HUVECs cultured on different collagen types.
- Cell proliferation was measured.
- Secretion of MMP-1, MMP-2, and vascular endothelial growth factor (VEGF) was analyzed.
Main Results:
- rMMP-7 dose-dependently accelerated HUVEC proliferation on type I and type IV collagen.
- MMP-7 upregulated the secretion of MMP-1 and MMP-2.
- MMP-7 did not stimulate VEGF secretion.
Conclusions:
- MMP-7 directly induces angiogenesis by promoting endothelial cell proliferation.
- MMP-7 represents a promising therapeutic target for anti-cancer strategies.