Modulation of Motility and Proliferation of Glioma Cells by Hepatocyte Growth Factor

• Published in: Cancer science 1997-06, Vol.88 (6), p.564-577
• Main Authors: Yamamoto, Shinji, Wakimoto, Hiroaki, Aoyagi, Masaru, Hirakawa, Kimiyoshi, Hamada, Hirofumi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Astrocytoma; Autocrine signalling; Base Sequence; Biological and medical sciences; Boyden chamber; Brain Neoplasms - pathology; Brain Neoplasms - physiopathology; Brain Neoplasms - surgery; c-Met protein; Cell culture; Cell Division - drug effects; Cell Movement - drug effects; Cell proliferation; DNA Primers; DNA, Neoplasm - biosynthesis; Female; Fibroblast growth factor 2; Glioblastoma - pathology; Glioblastoma - physiopathology; Glioblastoma - surgery; Glioma - pathology; Glioma - physiopathology; Glioma - surgery; Glioma cells; Growth factors; Growth Substances - pharmacology; Hepatocyte growth factor; Hepatocyte Growth Factor - biosynthesis; Hepatocyte Growth Factor - pharmacology; HGF; Humans; Immunohistochemistry; Invasion; Male; Medical sciences; Met; Middle Aged; Molecular Sequence Data; Motility; mRNA; Neurology; Paracrine signalling; Paraffin; Platelet-derived growth factor; Polymerase Chain Reaction; Proliferation; Proto-Oncogene Proteins c-met; Receptor Protein-Tyrosine Kinases - biosynthesis; RNA, Messenger - biosynthesis; Thymidine; Thymidine - metabolism; Transcription, Genetic; Tumor Cells, Cultured; Tumors of the nervous system. Phacomatoses
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.1997.tb00420.x

Invasive proliferation is a critical biological characteristic of gliomas. We evaluated the activities of hepatocyte growth factor (HGF) on proliferation and motility of glioma cells, comparing them with the effects of other growth factors (EGF, bFGF, PDGF‐BB, TGF‐βl). Seven primary culture lines all expressed c‐met and HGF mRNA, and secreted HGF. HGF stimulated 3H‐thymidine uptake of every glioma cell line (30 to 70% upregulation). Boyden chamber assay and scattering assay revealed that HGF promoted cell motility with chemokinetic and strong chemotactic activities. Concentric circle assay showed that HGF promoted two‐dimensional expansion (proliferation and motility) most strongly among the growth factors studied. Further, we analyzed 23 paraffin‐embedded sections of surgically resected gliomas (7 grade II, 8 grade III, and 8 grade IV) by immunohistochemistry. Expression of HGF and Met increased with malignant progression of gliomas, suggesting that gliomas stimulated their invasive proliferation by autocrine HGF production. Neurons and vasculature were HGF‐positive, and Met‐positive glioma cells gathered around them. The data indicate that neurons and vasculature, which are the main tracks of glioma invasion, augment chemotactic invasion and proliferation of gliomas by paracrine HGF secretion. Clearly HGF plays a critical role in invasive proliferation of glioma cells and it is therefore a candidate target of therapeutic intervention.