A recent study to disprove the idea that some cancer and immune cells can merge and form a new, more potent cancer cell, actually ended up proving the validity of the theory — scattered evidence for which has been accumulating for quite some time.
Biologist Alain Silk and colleagues from the Oregon Health and Science University presented their findings during a poster session at the recent American Society for Cell Biology Annual Meeting in New Orleans.
The researchers performed in vitro experiments in which colon cancer cells derived from a mouse model were cultured with macrophages — a type of immune (white blood) cell commonly found in many types of tumors (the name means “giant eater”). The two cell types were engineered with unique fluorescent markers so that the team could keep track of them and determine whether or not a cell merger had transpired. Following analysis of the cells, Silk et al were surprised to find that a small proportion of the cells had fused — forming hybrid cells.
“When I initially decided to do this I thought, ‘I’m going to disprove this idea.’” – Alain Silk, biologist, Oregon Health and Science University
Instead, Silk and colleagues ended up providing more evidence supporting this theory — a theory that was first postulated as far back as 1911 by German biologist Otto Aichel.
The hybrid cells — comprised of a fused female (mouse) cancer cell and a male macrophage — possessed chromosomal combinations from both types of cells (i.e., X and Y chromosomes) which strongly indicated that cell fusion had occurred.
Silk et al also conducted 70 cell “microenvironment” experiments and found that some of the hybridized cells developed altered adhesive capabilities. Gene expression profiles conducted on the hybrid cells confirmed the expression of genes from both of their parent cells, however, the profiles also showed that the merged cells expressed unique genes not expressed in the parent lines. This gene expression variability may account for the variability in adhesiveness. This is important as cell adhesion is related to a cancer cell’s mobility, which in turn is related to its metastatic potential.
Following this, the researchers exposed the hybrid cells to a variety of cell-signalling molecules known as cytokines which help to modulate the immune response. The hybrid cells showed a “growth advantage” after encountering some of these molecules. In a final experiment, Silk’s team injected the hybrid cells into mice — finding that tumor growth was more rapid than tumors grown from non-fused cells.
Assessing his team’s findings, Silk stated:
“It definitely supports the idea that fusion can result in phenotypic changes to cancer cells that enhance their growth.”
When normal cells evolve to a disease state, they typically do so via some type of genetic mutation. Cell hybridization, or fusion, may be one additional way that cancer cells mutate and thus gain advantageous capabilities (i.e., new phenotypes). Cell fusion may be yet another “trick” cancer cells have acquired to evade the body’s immune system.
Although this ‘proof of concept’ experiment is tantalizing, it does not provide definitive proof that this cancer-immune hybridization is in fact occurring (note: many cancer cells have elevated chromosome counts without under-going cell fusion). Further, these were in vitro (cell culture) experiments and do not necessarily parallel what goes on in vivo (in a living animal).
However, these results provide sufficient evidence to propel further study in live animal models. If supported, this fusion effect could explain how some tumor cells are able to metastasize more readily that others; the hybrid cells might be taking advantage of the greater growth potential of cancer cells and the greater mobility of macrophages.Silk et al plan on next investigating the behavior of these hybrid cells in the mouse’s circulatory system.
Macrophages are important components of the immune system and vital for destroying diseased cells. However, macrophages also secret key chemical signals which induce a “pro-inflammatory effect”. This effect — if left unchecked — has been found to be a precondition for various diseases, including cancer.
Further, macrophages, being immune cells, are ready-made to fuse with other cells, and tumor cells typically contain a great many macrophages (and cancer cells naturally fuse together). So, the idea that cancer cells and immune cells are capable of fusing would not seem so surprising.
Some source material (including quotes) for this post came from The Scientist article ‘Cancer and Immune Cells Merge’ by Kate Yandel
Research reference: A.D. Silk et al., “Spontaneous fusion with macrophages alters cancer cell phenotypes,” American Society for Cell Biology Annual Meeting (poster), 2013.
Top photo: (A macrophage of a mouse stretching its “arms” (pseudopodia) to engulf two particles, possibly pathogens. Trypan Blue Exclusion method; image not from the study by Silk et al) ; credit: Obli at en.wikipedia ; CC-BY-SA-2.0