Possible monocytic origin of chondrosarcoma: in vitro transdifferentiation of HLA-DR blood monocyte-like cells from a patient with chondrosarcoma, into neo-fibroblasts and chondrocyte-like cells

Abstract

Nodules and multilayered areas composed of fibroblasts and chondrocyte-like cells embedded in an abundant extracellular matrix appeared spontaneously in in vitro culture of mononucleated blood cells taken from a patient with chondrosarcoma. Using specific antibodies it was demonstrated that the neo-fibroblasts which developed in the culture resulted from a direct transdifferentiation of monocytes expressing HLA-DR specificity. The experiment was carried out twice, once before surgery and then two years later. In both cases the spontaneous transdifferentiation of HLA-DR monocytes into neo-fibroblasts was observed. Previously it was shown that normal monocytes were also able to give rise in vitro to neo-fibroblasts. However, the latter are normally rapidly destroyed by cell-cell contact with T-cells. Normal T-cells adhere to normal neo-fibroblasts by which they are finally engulfed. As a result, the neo-fibroblasts lose their fibroblastic shape, no longer adhere to their support and die. Therefore the abnormal proliferation and persistence of neo-fibroblasts in pathological situations such as the present case may result either from an intrinsic defect in monocytes, T-cells or both. The question is whether or not this transdifferentiation process observed in vitro accounts for the development of chondrosarcoma in vivo. The present results suggest that in vivo chondrosarcoma may start in a necrotic zone (resulting for instance from trauma) and attract HLA-DR monocytes, where they accumulate and transdifferentiate into neo-fibroblasts and chondrocyte-like cells. The uncontrolled transdifferentiation of these HLA-DR monocytes resulting from a dysregulation of the immune system is probably linked to the malignant process which may have a retroviral origin. The question is raised regarding the embryologic origin of this special sub-population of blood monocytes in which pluripotential capabilities are retained; its origin may differ from that of the other circulating monocytes.