This is the location of fluorescently labeled Fas-ligands (Fas-L) and caveolin (Cav-1) in the cell. The last image is the overlap of the Fas-L and Cav-1 (merge) channels. Obtained by laser confocal scanning microscopy. Photo: Vladimir Gogvadze

The disruption of a pathway initiating cell death delays the inevitable – and could eventually provide new avenues of cancer treatment, Russian scientists report in a Springer journal.

The Fas-ligand protein is a fundamental molecular building block in tumor necrosis. Fas-ligand needs to bond with a “death receptor” on the plasma membrane to start a series of reactions that ends with apoptosis, one natural mode of death. Caveolin, an integral protein in the membrane, is required for Fas-ligand to make its fatal connection.

By removing the binding sites on the Fas-ligand surface, the scientists removed most of the “killer activity” power of the cells, they report in Cell Death and Disease.

“The deletion of both caveolin-binding sites in Fas-ligand impairs its distribution between cellular membranes, and attenuates a Fas-ligand-induced cytotoxicity,” the study authors write.

The in-vitro models involved monitor the direct exposure of Fas-ligand to caveolin-1 to identify the location of its binding sites.

The researchers found two such sites.

The deletion of both, they found, disrupted the Fas-ligand routing to lipid rafts, and then stopped the process of death before the first molecular domino fell.

“These results suggest that caveolin-1 may regulate Fas-ligand location and, respectively, modulate Fas-ligand dependent cell death,” they write.

The materials employed in the experiments were from multiple species: mouse models and rabbit antibodies, and African green monkey kidney cells were used, along with continuous cell lines from vertebrates.

Another cell line used was the human cervical adenocarcinoma HeLa cells, the “immortal” cell line derived from patient Henrietta Lacks, who died in 1951.

Vladimir Gogvadze, the lead author, of the Lomonosov Moscow State University, said the experiments used “traditional cell and molecular biology methods.”

“The main value of our work is to disclose the mechanisms of cell death stimulation,” added Gogvadze. “In the future it will help to develop new strategies for the treatment of cancer.”