• 1 January 1978
    • journal article
    • research article
    • Vol. 91  (2) , 277-298
Abstract
Dunn osteosarcomas synthesize 2 times more alkaline phosphatase than Ridgway osteosarcomas, 3 times more than HeLa human cervical cancer cells, and 4-5 times more than rat or mouse fibroblast cell cultures. Implants of killed freeze-dried Dunn cell cultures into the thigh muscles are resorbed and replaced by normal cartilage, bone and bone marrow tissue, while implants of freeze-dried Ridgway cells are resorbed and replaced by fibrous tissue only. Outgrowths of normal muscle septum connective tissue cells onto the stroma of Ridgway tumors differentiate into fibrous tissue. Cultures of either tumor on a substratum of bone matrix stroma prepared from normal bone proliferate, assume a spherical shape and perpetuate the transformed osteoblast-like cell without forming attachments or adapting to the contour of the substratum. Outgrowths of muscle mesenchymal cells on the Dunn tumor stroma differentiate into cartilage. Dunn osteosarcoma cell cultures proliferate on the inside and produce deposits of normal bone on the outside of diffusion chambers. Killed freeze-dried cell cultures produce transfilter deposits of normal bone and bone marrow, but the quantity is significantly lower. On a substratum of cellulose acetate, outgrowths of muscle connective tissue will differentiate into cartilage when cell-free Dunn stroma is present under the organ culture grid. Tumorigenesis and normal cartilage and bone morphodifferentiation are antithetic, but tumor cells transfer a bone morphogen similar to the bone morphogenetic protein (BMP) of normal bone matrix. BMP recruits mesenchymal cells to proliferate and differentiate into cartilage and bone.