Research News
New Imaging Technique Reveals New Details About Metastasis
One recurring finding about malignant cells is that the fluidity of their outer membrane increases as the cells become metastatic. Now, using brightly fluorescent quantum dots, cancer researchers in Japan have begun teasing out the details of how molecules move around within the membrane as its fluidity changes, providing new insights into the functional dynamics of metastasis-associated membrane changes.
Kohsuke Gonda, of Tohoku University, and Hideo Higuchi, of the University of Tokyo, led the team of investigators that used nanometer-sized quantum dots and three-dimensional confocal microscopy to follow the movement of individual protein molecules within the cell membrane. For this study, the investigators labeled an antibody that binds to as protease-activated receptor 1 (PAR1), a membrane protein that promotes metastasis. The investigators constructed a new device that enabled them to image quantum dots in tumors in live animals. The results of their studies were published in the Journal of Biological Chemistry.
The investigators studied membrane dynamics by tracking the motion of quantum dot-labeled antibodies that attached themselves to PAR1. The researchers made their measurements in four different locations representing different stages of metastasis: far from the blood vessels in tumors, near blood vessels, in the bloodstream, and adhering to the inner wall of blood vessels in normal tissues near tumors. Data from these experiments revealed that membrane fluidity was low when tumor cells were either far from the blood vessel or when they were sticking to blood vessels near normal tissues. Cells in either location are not likely to be metastatic.
In contrast, membrane fluidity increased significantly as tumor cells neared blood vessels – they were preparing to enter the blood stream and travel to other organs – and reached a maximum while the cells were in the bloodstream, where they are likely preparing to colonize other tissues. The investigators found, too, that membrane fluidity was high in the tiny protrusions that metastatic cells develop to help them move about as they metastasize. The investigators note that this method is not only useful for studying membrane dynamics in live tumor cells, but might also be useful for studying how anticancer drugs affect metastasis and tumor growth.
This work is detailed in a paper titled, “In Vivo Nano-Imaging of Membrane Dynamics in Metastatic Tumor Cells Using Quantum Dots.” An abstract of this paper is available at the journal’s Web site.
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