Neutrophils prepare niche in the lung for breast cancer metastasis and colonization

Tumors are known to hijack and exploit body's normal function for its own purpose. This is especially true for immune system which often is a reverse-target for growing tumors. 

For example, new study published by journal Nature this week showed that neutriphil-derived leukotrienes [small lipid molecules] support lung metastasis and colonization by primary breast cancer cells.

Two reasons why this study was accepted in Nature: (1) to promote newly established The Francis Crick Institute based in London [Nature is a UK journal], (2) positive results with Zileuton (Zyflo®), an orally active inhibitor of 5-lipoxygenase and leukotrienes (LTB₄, LTC₄, LTD₄, and LTE₄).

First, using mouse model, the authors [it has just 2 authors, very rare] showed that metastasis of breast cancer cells to the lung were supported by neutrophils (genetic depletion of neutrophils in G-CSF^-/- or Ela2-Cre-DTA mice as well as antibody-mediated neutrophil depletion reduced tumor metastasis).

Next, the authors found that neutrophil-conditioned medium supported tumor growth in vitro.

It turned out that this tumor-promoting neutrophil-conditioned medium contained high levels of leukotrienes, an active lipid metabolites of 5-lipoxygenase enzyme pathway. 

Finally, using 5-lipoxygease deficient mouse or Zileuton (Zyflo®) treatment, the authors showed that blocking leukotrienes activity reduced lung metastasis (though Zileuton (Zyflo®) treatment was surprisingly more effective compared to KO mouse).

In summary, this study suggests that anti-leukotriene therapy already available in the market could provide anti-cancer benefits.

David Usharauli