Study on zebrafish paves way for new cancer treatment

WASHINGTON - The imaging of tumour growth in zebrafish has shed light on how newly formed cancer cells can co-opt the immune system into spreading the disease.

The work is leading the way for investigations into potential therapies for eliminating early-stage cancer in humans

Using different coloured fluorescent tags, scientists at the University of Bristol labelled immune cells and tumour-forming cells in the translucent zebrafish in order to track their behaviour and interactions by live cell imaging.

Tests showed that cancer cells are less likely to proliferate if white blood cells can be prevented from contacting the precursor cancer cells, suggesting that white blood cells have the ability to promote disease by providing some kind of growth signal.

Interestingly, the chemical compound that acts as a draw between the two sets of cells was shown here to be hydrogen peroxide - commonly used as a disinfectant or antiseptic, but also a natural by-product produced by the body’s metabolic process.

Paul Martin of the University of Bristol said, “By visualizing the earliest interactions between cancer cells and their host environment, we have shown that even from their earliest stages tumours don’t just avoid being destroyed by the immune system. Rather, they appear to court an immune response, co-opting the body’s innate immune system to aid and abet their growth.”

The team used a method to switch on the human oncogene, HRAS, in specific pigment cells (melanocytes) in the skin of early stage zebrafish embryos. Studies were carried out using zebrafish because they conserve many of the molecular and cellular components of tumour formation seen in mammals and are almost translucent, making it easy to see the cells as they move around and grow.

Researchers monitored the first hours and days of development and as the embryo grew, some of the cells were transformed, ie, made cancerous by HRAS. Those transformed cells were found to actively attract the innate immune cells.

The researchers got the same results, after inserting HRAS into different, mucous-secreting cells, and again when experimenting with a different oncogene, SRC. They discovered that the tumour cells produced hydrogen peroxide and that immune cells were drawn up the hydrogen peroxide gradient towards the cancer.

The researchers showed that the immune cells appear to engulf cancerous cells in a bid to destroy them. However, other cells formed cytoplasmic tethers linking them to cancerous cells and in some cases the cancerous cells appeared to drag the immune cells back when they started to leave the region.

In order to see whether the tumour was avoiding destruction or actually co-opting the immune cells, the researchers blocked the immune response in three different ways: they prevented the development of immune cells for the first three days of the zebrafish embryos’ life, and separately, they used two different strategies to limit hydrogen peroxide production. In each case, immune cells failed to migrate to the cancer site. And each time, when the immune response was blocked, fewer cancer cells formed.

The findings were published in open access journal PLoS Biology. (ANI)