title: Proliferation and invasion: plasticity in tumor cells.
abstract: Invasive and proliferative phenotypes are fundamental components of malignant disease, yet basic questions persist about whether tumor cells can express both phenotypes simultaneously and, if so, what are their properties. Suitable in vitro models that allow characterization of cells that are purely invasive are limited because proliferation is required for cell maintenance. Here, we describe glioblastoma cells that are highly invasive in response to hepatocyte growth factor/scatter factor (HGF/SF). From this cell population, we selected subclones that were highly proliferative or displayed both invasive and proliferative phenotypes. The biological activities of invasion, migration, urokinase-type plasminogen activation, and branching morphogenesis exclusively partitioned with the highly invasive cells, whereas the highly proliferative subcloned cells uniquely displayed anchorage independent growth in soft agar and were highly tumorigenic as xenografts in immune-compromised mice. In response to HGF/SF, the highly invasive cells signal through the MAPK pathway, whereas the selection of the highly proliferative cells coselected for signaling through Myc. Moreover, in subcloned cells displaying both invasive and proliferative phenotypes, both signaling pathways are activated by HGF/SF. These results show how the mitogen-activated protein kinase and Myc pathways can cooperate to confer both invasive and proliferative phenotypes on tumor cells and provide a system for studying how transitions between invasion and proliferation can contribute to malignant progression.
authors: Laboratory of Molecular Oncology, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503, USA.
authors: Chong-Feng
authors: CF
authors: Gao
authors: Qian
authors: Q
authors: Xie
authors: Yan-Li
authors: YL
authors: Su
authors: Julie
authors: J
authors: Koeman
authors: Sok Kean
authors: SK
authors: Khoo
authors: Margaret
authors: M
authors: Gustafson
authors: Beatrice S
authors: BS
authors: Knudsen
authors: Rick
authors: R
authors: Hay
authors: Nariyoshi
authors: N
authors: Shinomiya
authors: George F
authors: GF
authors: Vande Woude
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology; D017228:Hepatocyte Growth Factor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017228:Hepatocyte Growth Factor