Using xCELLigence assay, the interaction between two membrane proteins is shown to modulate the trans-endothelial migration of metastatic cells
A team of Italian scientists reported this week that blocking the interaction between urokinase receptor (uPAR) and formyl peptide receptor type 1 (FPR1) suppresses the ability of melanoma cells to migrate, invade through an extracellular matrix, and to burrow through a layer of endothelial cells. Within gene knockdown and overexpression experiments, Maria Motti and colleagues employed an xCELLigence Real-Time Cell Analysis instrument to continuously track the migration/invasion of melanoma cells. The continuous tracking of these processes in a non-invasive manner using gold biosensors enabled them to tease apart subtle differences in kinetic behavior that would have gone unnoticed in a conventional endpoint assay.
Melanoma currently affects more than 3 million people globally, resulting in ~60,000 deaths each year. Owing to its tendency to metastasize through the blood and lymphatic vessels, it is the most aggressive form of skin cancer. Although the five-year survival rate is 98% for patients with localized disease, this drops to just 17% once metastasis has occurred. To date, effective treatments for metastatic melanoma are lacking. Citing that there is a growing “awareness that cancer therapy should include, in addition to treatment of the primary tumor and established metastases, also the prevention of metastasis formation,” a focus of Motti’s team has been the disruption of key protein-protein interactions that facilitate melanoma cell migration along chemical gradients. In their newest paper, published in the Journal of Experimental & Clinical Cancer Research, these scientists demonstrated that overexpression of uPAR and FPR1, which is known to occur in melanoma and to contribute to disease progression, promote metastatic disease phenotypes within melanoma cell lines in vitro. Using either a peptide antagonist of the uPAR-FPR1 interaction or an antibody that targets uPAR, the authors were able to suppress melanoma cell migration and invasion. Importantly, the peptide antagonist used here was effective at nanomolar concentrations, had no impact on cell proliferation, and displayed high stability in serum due to the retro-inverso nature of its construction. On the basis of their findings Motti’s team suggests that disrupting the uPAR-FPR1 interaction may be a viable means of blocking the progression of metastasis in melanoma patients. Since the proportion of these patients who have metastases at the time of diagnosis is high, they suggest that “combining current therapy with a systemic anti-metastatic agent might considerably improve the outcome.”
Motti and coworkers’ full manuscript can be viewed here.
About xCELLigence® RTCA
xCELLigence Real-Time Cell Analysis (RTCA) instruments utilize gold biosensors embedded in the bottom of microtiter wells to non-invasively monitor the status of adherent cells using the principle of cellular impedance. In short, cells act as insulators – impeding the flow of a miniscule electric current between electrodes. This impedance signal is measured automatically, at an interval defined by the user, and provides an extremely sensitive readout of cell number, cell size, cell-substrate attachment strength, and cell invasion/migration. xCELLigence RTCA instruments are being used in both academia and industry for basic and applied applications ranging from cancer immunotherapy and cardiotoxicity to drug discovery and viral titer determination. To date xCELLigence has been used in more than 1,400 publications, which can be viewed in a searchable library.
About ACEA Biosciences
Founded in 2002, ACEA Biosciences is a pioneer in the development and commercialization of high performance, cutting edge cell analysis platforms for life science research. ACEA’s xCELLigence impedance-based, label-free, real-time cell analysis instruments and NovoCyte® flow cytometer are used in pre-clinical drug discovery and development, toxicology, safety pharmacology, and basic academic research. More than 2,000 instruments have been placed globally.
For further information please contact:
ACEA Biosciences, Inc.
Dr. Jeff Xue
Phone: 1-858-724-0928, x3075