Proliferation and invasion: plasticity in tumor cells

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Malignant tumors exhibit invasive and proliferative phenotypes, but simultaneous expression and properties remain unclear.
• Existing in vitro models struggle to characterize purely invasive cells due to proliferation requirements for maintenance.

Purpose of the Study:

• To investigate glioblastoma cells' invasive and proliferative phenotypes.
• To characterize cells expressing both phenotypes simultaneously.
• To elucidate the signaling pathways involved in conferring these phenotypes.

Main Methods:

• Selection of glioblastoma subclones with distinct invasive and proliferative capacities in response to hepatocyte growth factor/scatter factor (HGF/SF).
• Characterization of biological activities including invasion, migration, urokinase-type plasminogen activation, and branching morphogenesis.
• Analysis of signaling pathways, specifically MAPK and Myc, in response to HGF/SF.

Main Results:

• Highly invasive cells showed specific biological activities, while highly proliferative cells exhibited anchorage-independent growth and tumorigenicity.
• Highly invasive cells signaled via the MAPK pathway, whereas highly proliferative cells utilized the Myc pathway.
• Cells with both phenotypes activated both MAPK and Myc pathways in response to HGF/SF.

Conclusions:

• Hepatocyte growth factor/scatter factor (HGF/SF) can induce distinct invasive and proliferative phenotypes in glioblastoma cells.
• Cooperation between the mitogen-activated protein kinase (MAPK) and Myc signaling pathways confers both invasive and proliferative phenotypes.
• This study provides a model system to explore the transitions between invasion and proliferation in cancer progression.