Image Credit: Julio C. Valencia, NCI Center for Cancer Research
We think of our immune system as being on our side, and for the most part, it is. Leukocytes, also known as white blood cells, perform body-defending roles, ranging from promoting inflammation to direct ingestion of pathogens. Billions of these leukocytes are generated in the body each day.
But what happens when our immune system works against us? Scientists have known for some time that immune cells can be recruited by cells which are on the path to becoming cancerous. These pre-cancerous cells round up leukocytes from the bloodstream by acting like a wound, spitting out chemicals like hydrogen peroxide to dupe the immune cells into moving towards them. Once behind enemy lines, the leukocytes turn traitorous. They wrap around the pre-cancerous cells and feed them with a growth factor called PGE2, driving rapid proliferation and ultimately formation of a tumour.
Leukocytes are usually found inside blood vessels, while pre-cancerous cells tend to reside in the epithelial tissues which lie on top. A basement membrane separates the two. To feed the pre-cancerous cells, leukocytes must breach this barrier. New research shows that this can happen opportunistically via tiny perforations in the membrane. If a pre-cancerous cell is close to such a perforation, it is able to hoodwink leukocytes into slipping through the gap. As such, pre-cancerous cells like these are more likely to become tumours than those with no way of recruiting leukocytes.
Pores in the basement membrane can arise in other ways too. Once a tumour gets big enough, it starts eroding the basement membrane using digestion enzymes. This allows it to grow even faster by enlisting further leukocytes. In addition, mechanical damage of the epidermis via wounding can open up much larger pores than are usually present. Again, this facilitates more rapid proliferation of nearby pre-cancerous cells into tumours.
This presents a problem, because diagnostic needle biopsies will naturally open up large holes in the basement membrane. Invasive surgery has a similar effect. In both cases, tissue damage may contribute to the formation of a tumour from pre-cancerous cells by providing a portal through which double-crossing leukocytes can pass in order to feed the cancer.
From a clinician’s perspective, this means care must be taken in making decisions regarding surgery, especially in cases where surgery may not remove all of the cancerous cells. There is a delicate balance between the need to remove a tumour and the need to avoid provoking further growth.
There is also a clear need for refining therapeutic drugs which can counter the response outlined in this research. This could be dampening it or targeting the growth factors the pre-cancerous cells need in order to proliferate. The deeper the understanding scientists have of the many processes and pathways involved in cancer progression, the more refined and effective our treatments will become.