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Publication : Stromal metalloproteinase-9 is essential to angiogenesis and progressive growth of orthotopic human pancreatic cancer in parabiont nude mice.

First Author  Nakamura T Year  2007
Journal  Neoplasia Volume  9
Issue  11 Pages  979-86
PubMed ID  18030366 Mgi Jnum  J:169286
Mgi Id  MGI:4940190 Doi  10.1593/neo.07742
Citation  Nakamura T, et al. (2007) Stromal metalloproteinase-9 is essential to angiogenesis and progressive growth of orthotopic human pancreatic cancer in parabiont nude mice. Neoplasia 9(11):979-86
abstractText  We determined whether host matrix metalloproteinase (MMP) 9 is essential to angiogenesis and to the growth of L3.6pl human pancreatic cancer cells implanted into the pancreas of wild-type (MMP-9(+/+)) and knockout (MMP-9(-/-)) nude mice. Four weeks after tumor cell injection, pancreatic tumors in MMP-9(+/+) mice were large, had many blood vessels, and contained many macrophages expressing MMP-9. In contrast, pancreatic tumors in MMP-9(-/-) mice were significantly smaller, had few blood vessels, and had few macrophages. Next, we parabiosed MMP-9(+/+) mice with MMP-9(+/+) mice, MMP-9(-/-) mice with MMP-9(-/-) mice, and MMP-9(+/+) mice with MMP-9(-/-) mice. Two weeks after parabiosis, we implanted L3.6pl cells into the pancreas of the recipient mouse in each pair. Four weeks later, the mice were necropsied. The parabiosis experiment revealed a direct correlation between intratumoral MMP-9(+/+) expressing macrophages, angiogenesis, and progressive tumor growth. Because the expression of MMP-9 by L3.6pl tumor cells was similar in all parabionts, the data clearly demonstrate a major role for host-derived MMP-9 in angiogenesis and in the growth of human pancreatic cancer in the pancreas of nude mice.
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