Elsevier

Neoplasia

Volume 9, Issue 11, November 2007, Pages 979-986
Neoplasia

Stromal Metalloproteinase-9 Is Essential to Angiogenesis and Progressive Growth of Orthotopic Human Pancreatic Cancer in Parabiont Nude Mice*

https://doi.org/10.1593/neo.07742Get rights and content
Under a Creative Commons license
open access

Abstract

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.

Keywords

MMP−9
parabiosis
pancreatic cancer
angiogenesis
orthotopic model

Abbreviations

GFP
green fluorescent protein
MMP
matrix metalloproteinase
MVD
microvessel density
PBS
phosphate-buffered saline
PCR
polymerise chain reaction
PECAM-1
platelet-endothelial cell adhesion molecule-1

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*

1This research was supported, in part, by Cancer Center Support Core grant CA16672 and SPORE in Prostate Cancer grant CA90270 from the National Cancer Institute, National Institutes of Health.