Malignant mesothelioma (MM) cells can differentiate into bone-like cells, according to a study published in Scientific Reports, a finding that may open new possibilities for therapeutic approaches against MM.
The study, “A Subset Of Malignant Mesothelioma Tumors Retain Osteogenic Potential,” was conducted by S. M. Lansley, PhD, and colleagues from the Harry Perkins Institute of Medical Research.
During embryonic development, there are essentially three layers of cells that give rise to the different parts of the body. The most external layer (ectoderm) will originate skin cells and the central nervous system (spinal cord and the brain); the middle layer (mesoderm) will produce cells of various organs, including blood vessels, heart, lungs, kidneys, bones and muscles; and the inner layer (endoderm) produces organs of the gastrointestinal tract.
At a certain point in embryonic development, all these organs share a common ancestry, but become different from each other as cells migrate to different environments within the body, where they differentiate into their final form and function.
MM derives from cells that once belonged to that middle layer, called the mesothelial cells. Previous studies have shown that mesothelial cells differentiate into cells of similar lineage. Indeed, certain MM patients present signs of bone- and cartilage-like cells, that share the same origin, which further supports this idea.
“We have previously demonstrated that normal mesothelial cells can differentiate to [bone-like cells] and therefore hypothesize that all cells of mesothelial origin, including MM, are responsible for the observed osseous differentiation and mineralized bone formation in MM tumors,” the researchers wrote.
Consistent with such findings, the researchers observed that MM tumors often presented areas of mineralized bone formation. This was found both in the biopsy of a 27-year-old woman with malignant mesothelioma and in more than 20% of MM mouse models.
The team then used different cell lines of human MM cells to understand if culture media containing molecular factors that promote the formation of bone cells could induce MM cells to transform into bone cells. Results indicated that, indeed, in such an environment, MM cells produced bone cells in vitro and expressed molecular markers associated with bone formation.
Researchers then used dexamethasone, a drug that has been used to induce the differentiation of bone cells from different cell types in vitro, to see if this treatment could have the same effect in MM cells. However, the results were negative.
Although it is not yet known how the presence of unusual cells in MM tumors may affect patient prognosis, the discovery that MM cells can turn into bone-like cells may represent a relevant finding.
“[I]f a positive correlation between heterologous elements in MM and patient survival exists, inducing MM cells to differentiate into non-malignant [cell types] may be a treatment option,” the researchers wrote. “Differentiation therapy has already been used in several different cancers to induce terminal differentiation in cancer stem cells to decrease cell proliferation and halt tumor progression.”