Thursday, October 30, 2014

’Dialogue’ with normal cells helps cancer cells spread tumours elsewhere: study

TORONTO — Canadian scientists have made a major discovery about how cancer spreads: tumour cells appear to co-opt normal cells around them, in effect “talking” them into helping the cancer set up shop in other parts of the body.
The process, called metastasis, is what often makes malignancies so challenging to treat — and typically more deadly.

“People often think of cancer as this separate tissue, sort of like a foreign invader, a thing that’s sitting inside that’s separate from their normal body,” said principal investigator Jeff Wrana, a molecular biologist at the Samuel Lunenfeld Research Institute in Toronto.
“But, in fact, the cancers are intimately communicating in a dialogue with the normal cells around them,” he said. “So basically, the normal cells are passing signals to the tumour cells and the tumour cells are passing signals to the normal cells.”
Working with human breast cancer cells in the lab, Wrana and colleagues found that tumour cells get sets of instructions in the form of protein “messages” passed between healthy and cancerous cells.
It’s been known for a while that communication existed between these cell types, but it was thought it was akin to “words” or incomplete “sentences.”
“But what we discovered was that the normal cells were basically sending an entire paragraph of instructions to the tumour cells,” said Wrana.
“And these instructions were actually telling the tumour cells how to use its own machinery to invade and metastasize, to spread throughout the body.”
The protein that does the talking is part of tiny fragments of cells called exosomes. In cancer, the tumour cell releases exosomes to influence neighbouring cells — and those nearby normal cells secrete exosomes that help tumour cells to spread.
“The tumour cells are kind of tweaking the normal cells and making them misbehave,” explained Wrana. “Then these normal cells start producing things that actually help the tumour cell.”
The researchers, who were at first surprised and skeptical of their finding, also looked for the phenomenon in lab mice bred as a model for human breast cancer.
They found the communication between normal and tumour cells also occurred in the animals. And Wrana said the same process would go on in people.
“And it’s that spreading metastases, for instance to the lung, that is the cause of death for a vast number of cancer patients.”
Metastases that originate from a primary cancer site in other organs — for instance, a prostate tumour that transfers its cells into bone —likely are activated in a similar way, said Wrana, whose lab will next look for this cell-to-cell dialogue in invasive bladder cancer.
He said the discovery of the exosomes’ role is important because it gives researchers a new treatment target: “If we can interfere with that, then we can block the ability of the cancer cells to spread out of the primary site.”
The research team is looking to develop drugs known as biologics that would block this signal pathway between cells.
“Instead of only targeting the primary tumour, we can now pinpoint the cells in the tumour’s environment that are responding to the tumour and target those too,” said Valbona Luga, a co-author of the study published Thursday in the journal Cell.
“We hope to use our new knowledge of the tumour’s immediate surroundings to intercept its signals to cancer cells, and by doing so, drastically impede tumour spreading,” she said.

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