Journal
NEOPLASIA
Volume 9, Issue 11, Pages 979-986Publisher
ELSEVIER SCIENCE INC
DOI: 10.1593/neo.07742
Keywords
MMP-9; parabiosis; pancreatic cancer; angiogenesis; orthotopic model
Categories
Funding
- NCI NIH HHS [CA16672, P30 CA016672, CA90270, P50 CA090270] Funding Source: Medline
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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 MMP9 in angiogenesis and in the growth of human pancreatic cancer in the pancreas of nude mice.
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