HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity.

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• Hepatocyte growth factor/scatter factor (HGF/SF) regulates cellular processes like adhesion and migration.
• Invasive growth is a critical step in cancer metastasis.

Purpose of the Study:

• To investigate the role of HGF/SF in promoting invasive growth in MDA-MB-231 carcinoma cells.
• To elucidate the molecular mechanisms underlying HGF/SF-induced cell adhesion and invasiveness.

Main Methods:

• Treatment of MDA-MB-231 cells with HGF/SF and epidermal growth factor (EGF).
• Assays for cell adhesion, migration, and invasiveness through extracellular matrix proteins and basement membranes.
• Analysis of integrin expression, clustering, and function using function-blocking antibodies.
• Investigation of the involvement of the PI3-K pathway.

Main Results:

• HGF/SF, but not EGF, significantly promoted cell adhesion to laminins, fibronectin, and vitronectin via a PI3-K-dependent mechanism.
• Increased cell adhesion correlated with enhanced invasiveness through matrix proteins and basement membranes.
• HGF/SF induced clustering of integrins beta1, beta3, beta4, and beta5 at adhesion sites, increasing their avidity for ligands without altering membrane expression.
• Extracellular matrix protease activity was not substantially affected by either factor.

Conclusions:

• HGF/SF promotes cancer cell adhesion and invasiveness by upregulating integrin avidity for extracellular matrix ligands.
• The PI3-K pathway plays a crucial role in HGF/SF-mediated cell adhesion and subsequent invasiveness.
• Integrin clustering and increased avidity, rather than altered expression, are key mechanisms for HGF/SF-induced invasive growth.