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Page updated at 12:43:23 PM on Monday, May 21st, 2012

Polarized cell structures in metastasis: coordination of the plasma, membrane, cytoskeleton and organelles

Funded with €65,100.00 for 36 months (from January, 2011 to December, 2013) by FIRC within Pierluigi Meneghelli FIRC Scholarship 2012-2014

Person in charge: Blaine Bisel
LENS members: Martino Calamai

Quantitative fluorescence and multiphoton optical microscopies to understand the influence of cell structures on cell migration processes in cancer metastatis.

Metastasis is the leading cause of death from cancer. A central requirement for the development of metastasis is the ability of cancer cells to migrate out of the original tumor, through connective tissues, and into blood vessels before finally settling into a secondary site. While much is known about the biochemistry of membrane receptors and key signal transduction pathways activated during cell polarization and migration, less is known about the mechanisms controlling the structural reorganization essential for cell polarization and migration.

Polarized cultured cells form the model system for migration, one of the processes responsible for metastasis in cancer. Red: quantum dots labeling GM1 gangliosides in the plasma membrane; Green: antibody probe of GM130 in the Golgi apparatus; Blue: Hoechst stain of the nucleus.

This project is focused on how key cell structures, including membrane rafts, the Golgi apparatus and mitochondria, influence cell migration. We will begin by examining the mechanisms controlling membrane asymmetry at the leading edge of polarizing epithelial cells. We will then consider how membrane organization influences the polarization of intracellular organelles, including the Golgi apparatus and mitochondria, and vice versa. We will examine precisely which characteristics of cell polarization are essential for cell migration. Finally, we will apply the insights gained to the investigation of differences in polarization and migration between specific human cancer cell lines, with special attention paid to recognizing patterns leading to increased or decreased invasiveness.

These goals will be accomplished with a combination of techniques from cell biology, molecular biology and quantitative fluorescence microscopy in addition to innovative multiphoton optical microscopy techniques that allow for the visualization and direct manipulation of subcellular structures. A better understanding of the fundamental processes of polarization and migration, and of those processes which are hijacked in cancer, will improve the ability to design novel targeted drugs for the prevention and treatment of metastasis.

Publications

Only publications with LENS-affiliated authors are listed and for now there is no one.