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Am. J. Respir. Cell Mol. Biol., Volume 24, Number 5, May, 2001 556-562

Hepatocyte Growth Factor Promotes Tumor Growth in a Novel In Vivo Model of Human Lung Cancer

Joseph M. Pilewski, Thomas S. Bumbalo III, Autumn Gaither Davis, and Jill M. Siegfried

Departments of Medicine, Cell Biology and Physiology, and Pharmacology, University of Pittsburgh; and Lung Cancer Basic Science Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

Significant progress has been made toward identifying growth factors that display autocrine or paracrine effects on the growth of lung cancer cells. Determining the in vivo relevance of specific growth factors on lung tumor formation, however, has not often been demonstrated in laboratory models. Although hepatocyte growth factor (HGF) has been shown to have mitogenic and motogenic effects on human lung cancer cells in vitro, and to have prognostic importance in patients with lung cancer, the effects of HGF on tumor behavior in vivo remain unknown. We therefore developed an airway tumor xenograft model that allowed us to test the hypothesis that HGF promotes human non-small cell lung cancer (NSCLC) growth in vivo. Human airway tumor xenografts were created in Severe Combined Immunodeficient mice by injecting human lung adenocarcinoma cells into human bronchial segments. After determining the optimal times for tumor-cell injection and the time course of tumor growth, we evaluated the effects of HGF on tumor growth by injecting recombinant HGF, or saline as a control, into the lumen of tumor xenografts for 10 consecutive days. Histologic evaluation 2 to 3 wk later revealed that the HGF-injected xenografts had a significantly greater tumor volume and more tumor cells were located in the submucosal space than were found in the saline-injected xenografts. These data demonstrate the usefulness of this novel in vivo model to study NSCLC, and show that HGF promotes both the growth and invasion of human lung cancer in vivo.

Abbreviations: hematoxylin and eosin, H&E; hepatocyte growth factor, HGF; non-small cell lung cancer, NSCLC; Severe Combined Immunodeficient, SCID.




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