Brain cancer cells form network to become resistance to therapy

Brain cancer cells form network to become resistance to therapy

Cancer cells form extremely thin and long extensions of their cellular membrane, which they use to constantly scan the healthy brain, thus invading and colonizing it. As the tumor grows, the cancer cells use these extensions to interconnect to a large network where they communicate intensively and via long distances, making astrocytomas appear like highly complex, organ-like entities.

"Our first thought was: this looks like the formation of a new brain within the existing one," author said. "The tumor cells were interconnected in a network that resembles the ones we know of neurons and other cell types in the brain."

The investigators also found this network of tumor microtubes in tissue samples from brain cancer patients. The more the cancer cells were interconnected, the more malignant and resistant the tumor subtype was.

The scientists therefore hypothesized that the tumor microtube networks must be linked to therapy resistance. They observed that the tumors in fact recognize damage to the network and repair it immediately. Radiation therapy - the standard treatment in glioblastoma - fails to kill mainly the tumor cells that are part of the network, whereas cancer cells outside the network die.

How do the tumor cells form these extraordinary membrane extensions? An analysis of the gene activities in tumor tissue from 250 brain cancer patients provided a clue. For building their network, the cancer cells make use of specific molecular signaling pathways that are normally active during early development of the nervous system.

Experiments in which the scientists blocked these pathways in mice showed that the animals subsequently developed smaller tumors with fewer interconnections that responded very sensitively to radiotherapy.