Findings from recent research conducted by Dr. Jérôme Paggetti, Dr. Etienne Moussay and colleagues at the Luxembourg Institute of Health have revealed how leukemia cells manipulate surrounding healthy cells.
The Department of Oncology at the University's Laboratory of Experimental Cancer Research is led by Dr. Guy Berchem, who was recently appointed to the Board of Directors at Luxembourg's newly-established National Institute of Cancer. The Laboratory's research unveiled how leukemia cells release small vesicles called exosomes which alter the properties of the surrounding healthy cells in bone marrow and lymph nodes to create a favourable environment for their survival and proliferation.
Chronic lymphocytic leukemia (CLL) is a cancer of the blood originating in bone marrow cells strains which then spread to other organs through the blood. This type of leukemia mainly affects adults over the age of 50, and the slow progression of the disease means that those affected may not exhibit symptoms for several years of having the disease. LLC only develops in an environment that promotes tumour proliferation and in which the immune defense is inhibited.
Dr. Moussay and his team have been studying the interaction of leukemic cells and adjacent cells at the molecular level. For the study, which was recently published in international medical journal 'Blood', the researchers focused on the role of exosomes produced by leukemic cells. These exosomes are small vesicles, or sacs, filled with a complex mixture of molecules, including proteins and small nucleic acids.
"Studies on other types of cancer have shown that exosomes secreted by cancer cells are absorbed by surrounding healthy cells and the molecules introduced cause changes in favour of tumour growth," explained Dr. Moussay.
Dr. Paggetti added: "In our study we have analysed, for the very first time, the content of exosomes produced by the leukemic cells of CLL and we investigated the effect of these exosomes on the tumour microenvironment."
To perform the experiments, leukemia cells in culture derived from patient samples were used. The researchers observed that the released exosomes were internalised by the stromal cells found in the tumour microenvironment, especially by the cells lining the inner wall of blood vessels.
"We have seen that the molecules issued by exosomes alter the properties of target cells," stated Dr. Moussay. "The stromal cells then behave just like the tumour cells. They start to produce a large amount of cytokines. These are signalling molecules that induce inflammation, a very favourable condition for the survival of leukemia cells."
This new knowledge will in turn be used in the development of treatments and therapies for the disease. Dr. Moussay concluded:
"We have already begun to study whether targeting the interaction between exosomes and stromal cells could strengthen current therapeutic strategies. We could start thinking about developing treatments that block the merging of exosomes and stromal cells or that inhibit the secretion or production of exosomes from tumour cells."
The publication of these results was due to a collaboration between the research unit 'Proteomics and Genomics Research Unit'; the IBBL Institute of Luxembourg at the Institute of Health; the Centre Hospitalier Luxembourg; and two well-known international oncology research sites, the German Research Centre on Cancer DKFZ in Heidelberg and the French cancer research centre Gustave Roussy in Villejuif.
Photo by Luxembourg Institute of Health (Microscopic image of exosomes (green) inside of a cell (cell skeleton in red and cell nuclei in blue))
