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

Abstract

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.

Plasma Hepatocyte Growth Factor Elevation May Be Associated with Early Metastatic Disease in Primary Lung Cancer Patients

“…HGF promotes tumor growth in vivo models of a human lung cancer cell line in which cells are seeded into the lumen of airways. 26) This study suggests that HGF may result in tumor growth after one administration.…”

“…Many studies confirm HGF activity in cancer cells both in vitro and in vivo. 4,7,8,10,26) In vitro experiments suggest that only 5 to 10 ng/mL of HGF is sufficient to activate tumor cell activity, leading to invasion or metastasis. 7,10) Moreover, circulating HGF may have direct effects on micro-metastatic lesions.…”

Hepatocyte growth factor and other fibroblast secretions modulate the phenotype of human bronchial epithelial cells

“…Traditionally, subepithelial fibroblast hyperplasia is regarded as a pathological feature of airway remodeling and believed to contribute to airway luminal narrowing in obstructive airway diseases. Furthermore, heightened levels of HGF are known to promote bronchial neoplasia (35,40,44,50). Because subepithelial fibroblasts elaborate factors that increase the rate of wound closure and augment ciliogenesis, we speculate that subepithelial fibroblast proliferation following epithelial injury may have a beneficial role in airway epithelial repair.…”