Orthotopic and ectopic chondrogenesis and osteogenesis mediated by neoplastic cells

In mice, tumors of various origins have been found to stimulate cambium layer cells of periosteum/ perichondrium of adjacent orthotopic bone or cartilage to proliferate and/or differentiate into osteoblasts or chondroblasts. Tumors may induce new bone and/or cartilage formation. In progressively growing tumors the osteogenic/chondrogenic activity is gradually surpassed by the resorptive processes mediated either by osteoclasts, directly by tumor cells, or by tumor stroma. In regressing tumors, however, the deposits of new bone remained unresorbed, resulting in a permanent gain of bone mass. In human subjects, similar changes were observed in bone adjacent to carcinoma development. Stimulation of periosteal bone formation was observed at earlier stages of the disease, while bone resorption mainly by tumor cells and their stroma was observed in later stages of tumor development. The unresponsiveness of the heterotopically-induced bone to the Moloney sarcoma virus, in contrast to the response of orthotopic bone clearly indicates that ectopic bones do not develop a true periosteum.