Chronic Inflammation and Tissue Damage Recruits Stem Cells, Which Accumulate Mutations and May Become Transformed
Although there is a clustering of diagnosis of malignancy around the time of initial diagnosis of myositis, this is not universally true. Some tumors are diagnosed after the rheumatic syndrome becomes well established. This is particularly true for scleroderma and Sjögren's syndrome-associated malignancies.[3] Possible explanations of this observation include: (i) malignancy developing at later times is due to drug toxicity; (ii) the appearance of malignancy is unrelated to the rheumatic syndrome; (iii) tumor escape from the effective immune response; and (iv) increased stem-cell recruitment and mutation in the environment of chronic inflammation and repair. Defining which of these mechanisms are relevant to human myositis will be extremely challenging. Patient population studies on subtypes of rare phenotypes will be very difficult to pursue. Even with new molecular diagnostic techniques that can detect tumors at very early stages, defining silent tumors before they emerge is not yet feasible in large scale. Very little is known about stem-cell recruitment to the chronically inflamed microenvironment or on their behavior and changes at that site. A recent study by Houghton and colleagues[4] using a mouse model demonstrates a very striking connection between chronic inflammation, hematopoietic stem-cell recruitment and mutation, and cancer formation in the inflamed target tissue. These authors showed that chronic Helicobacter pylori infection stimulates the recruitment of bone marrow derived stem cells (BMDC) into the gastric mucosa, which engraft permanently into the tissue stem-cell niche, assuming functions of the former. In the inflammatory microenvironment generated by H. pylori, the engrafted BMDCs accumulate mutations, and appear to be the cells that give rise to the gastric tumors arising in these animals. Understanding the role of hematopoietic stem cells in tissue repair in various target organs in the rheumatic diseases (including myositis) is a major priority.
Curr Opin Rheumatol. 2006;18(6):618-619. © 2006 Lippincott Williams & Wilkins
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