By Allan Mai ‘20

A sure sign of the progression of cancer occurs when tumor cells from the initial site of development breaks off and enters the bloodstream, invading other healthy tissue. A recently published study conducted by Barbara Szczerba and her team from the Cancer Metastasis Lab at the University of Basel found that circulating tumor cells (CTCs) are associated with white blood cells, especially neutrophils. Their discovery was particularly surprising due to neutrophils’ traditional role in the human body as the most abundant of the immune-cell types in the blood and of fighting infections.

At the onset of the experiment, the researchers isolated CTCs from CTC-neutrophil clusters and injected them into a group of tumor-free mice; they also injected the clusters themselves into yet another group of mice. They observed that the second group of rats – those that were infected with the clusters – had a higher chance of metastasis than the mice that were exposed to just the CTCs. Researchers also noted that a third group of mice – mice that had been depleted of neutrophils prior to being injected with CTCs – experienced the least metastasis.

In a second experiment that studied samples from 70 people diagnosed with late stage breast cancer, the researchers found that breast cancer patients with CTC-neutrophil clusters deteriorate at a more rapid rate. Building on these observations, Szczerba and her team associated CTCs with neutrophils and found that these cells expressed genes associated with cell proliferation at a much higher frequency than do CTCs that are not clustered with neutrophils. In other words, CTC-neutrophil clusters are already primed to spread throughout the body. The researchers also noted that CTC-neutrophil cancer patients had frequent mutations at the TLE1 gene; these mutations are suspected to enhance cluster formation.

The researchers proposed an explanation for why these CTC-neutrophil clusters exacerbate cancer growth: while the bloodstream is a hostile environment for free floating cancer cells, neutrophils escort cancer cells in the bloodstream to secondary sites, thereby protecting these cells. They expect that their findings will modify current approaches to treating certain types of cancers.

References

1. B. Szczerba, et. al., Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature, (2019). doi: 10.1038/s41586-019-0915-y.  
2. Image retrieved from: https://www.pexels.com/photo/pink-sphere-splashed-by-green-liquid-45239/