Matrix Metalloproteinase-9 from Bone Marrow–Derived Cells Contributes to Survival but not Growth of Tumor Cells in the Lung Microenvironment

DOI PDF 被引用文献5件
  • Heath B. Acuff
    Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee
  • Kathy J. Carter
    Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee
  • Barbara Fingleton
    Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee
  • D. Lee Gorden
    Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee
  • Lynn M. Matrisian
    Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee

書誌事項

公開日
2006-01-01
DOI
  • 10.1158/0008-5472.can-05-2502
公開者
American Association for Cancer Research (AACR)

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<jats:title>Abstract</jats:title><jats:p>The role of specific stromal-derived matrix metalloproteinases (MMPs) was analyzed in experimental metastasis assays in wild-type and either MMP-9, MMP-7, or MMP-2 null mice. MMP-9 null mice showed an 81% reduction in Lewis lung carcinoma tumor number, whereas MMP-7 null mice showed a 42% increase in tumor number, and there was no difference in tumor number in MMP-2 null mice compared with wild-type controls. Similarly, in an orthotopic model of lung cancer, 50% fewer MMP-9 null mice were able to establish tumors in the lung compared with control mice, although the size of the tumors was not different. The effect of MMP-9 on lung tumor colonization was dependent on the expression of MMP-9 from bone marrow–derived cells and is most likely contributed by neutrophils. To examine temporal effects of stromal MMP-9, bioluminescence imaging from luciferase-expressing human lung cancer–derived A549 cells revealed that there were fewer tumor cells in the lungs of MMP-9 null mice as early as 19 hours after injection compared with control mice, with no difference in subsequent growth rates. Six hours after injection of tumor cells, MMP-9 null mice showed a 4-fold increase in the percent of tumor cells undergoing apoptosis compared with control mice. We conclude that MMP-9 from the bone marrow contributes to the early survival and establishment of tumors in the lung and has no effect on subsequent growth. These results provide insights into the failure of MMP inhibitors in clinical trials in patients with late-stage lung cancer. (Cancer Res 2006; 66(1): 259-66)</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 66 (1), 259-266, 2006-01-01

    American Association for Cancer Research (AACR)

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