ATP bioluminescence (BLI and cancer #2)

Read also BLI and cancer #1

This is the post topic selected in the first Reportergene poll. Enjoy it!

Within a cell, ATP is both the energy currency inside and an extracellular messenger outside. Recent data show that adenosine concentration is much higher in the insterstitium (outside) of solid tumors compared to healthy tissues, and this information corroborates the growing awareness that tumor cells build up a 'self-advantage' micro-environment that limits the anti-tumor immune response. Thus, understanding ATP concentration dynamics outside the cells is a must for upcoming cancer research, particularly if this can be done in the context of the natural tissue.
The italian researcher Patrizia Pellegatti and colleagues from Ferrara University, have engineered a chimeric plasma membrane-targeted luciferase that allows in vivo real-time imaging of extracellular ATP. With this novel probe, they have measured the ATP concentration within the niche of several experimentally-induced tumors. How they did it?

They previously engineered a chimeric luciferase-folate receptor construct in which they appended to luciferase cDNA the targeting sequences (leader sequence and GPI anchor) derived from the folate receptor. This novel probe, named pmeLUC (plasma membrane luciferase) is in fact targeted to and retained at the plasma membrane thus detecting ATP in the aqueous layer close to the cell surface.

So-called "reporter genes" are in fact reporting more than transcriptional activity, and some companies are exploring this new market sector.

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Pellegatti, P., Raffaghello, L., Bianchi, G., Piccardi, F., Pistoia, V., & Di Virgilio, F. (2008). Increased Level of Extracellular ATP at Tumor Sites: In Vivo Imaging with Plasma Membrane Luciferase PLoS ONE, 3 (7) DOI: 10.1371/journal.pone.0002599