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. 1978 May;91(2):277–298.

Osteogenesis and chondrogenesis in transplants of Dunn and Ridgway osteosarcoma cell cultures.

H Hanamura, M R Urist
PMCID: PMC2018200  PMID: 274082

Abstract

Dunn osteosarcomas synthesize 2 times more alkaline phosphatase than do Ridgeway osteosarcomas, 3 times more than do HeLa cells, and 4 to 5 times more than do 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 Ridgeway cells are resorbed and replaced by fibrous tissue only. Outgrowths of normal muscle septum connective tissue cells onto the stroma of Ridgeway 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. Outgrwoths 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 (not tumorous 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amitani K., Nakata Y. Characteristics of osteosarcoma cells in culture. Clin Orthop Relat Res. 1977 Jan-Feb;(122):315–324. [PubMed] [Google Scholar]
  2. Amitani K., Nakata Y. Establishment and alkaline phosphatase activity of clonal cell lines of murine osteosarcomas. A preliminary study. Clin Orthop Relat Res. 1975 Nov-Dec;(113):164–167. doi: 10.1097/00003086-197511000-00026. [DOI] [PubMed] [Google Scholar]
  3. Amitani K., Nakata Y., Stevens J. Bone induction by lyophilized osteosarcoma in mice. Calcif Tissue Res. 1974;16(4):305–313. doi: 10.1007/BF02008238. [DOI] [PubMed] [Google Scholar]
  4. Amitani K., Nakata Y. Studies on a factor responsible for new bone formation from osteosarcoma in mice. Calcif Tissue Res. 1975;17(2):139–150. doi: 10.1007/BF02547286. [DOI] [PubMed] [Google Scholar]
  5. Anderson H. C. Osteogenetic epithelial-mesenchymal cell interactions. Clin Orthop Relat Res. 1976 Sep;(119):211–223. [PubMed] [Google Scholar]
  6. Auerbach R. The use of tumors in the analysis of inductive tissue interactions. Dev Biol. 1972 May;28(1):304–309. doi: 10.1016/0012-1606(72)90146-7. [DOI] [PubMed] [Google Scholar]
  7. Crick F. Diffusion in embryogenesis. Nature. 1970 Jan 31;225(5231):420–422. doi: 10.1038/225420a0. [DOI] [PubMed] [Google Scholar]
  8. FINKEL M. P., BISKIS B. O. The induction of malignant bone tumors in mice by radioisotopes. Acta Unio Int Contra Cancrum. 1959;15(1):99–106. [PubMed] [Google Scholar]
  9. Finkel M. P., Biskis B. O., Jinkins P. B. Virus induction of osteosarcomas in mice. Science. 1966 Feb 11;151(3711):698–701. doi: 10.1126/science.151.3711.698. [DOI] [PubMed] [Google Scholar]
  10. Firschein H. E., Urist M. R. The induction of alkaline phosphatase by extraskeletal implants of bone matrix. Calcif Tissue Res. 1971;7(2):108–113. doi: 10.1007/BF02062599. [DOI] [PubMed] [Google Scholar]
  11. Friedman B., Heiple K. G., Vessely J. C., Hanaoka H. Ultrastructural investigation of bone induction by an osteosarcoma, using diffusion chambers. Clin Orthop Relat Res. 1968 Jul-Aug;59:39–57. [PubMed] [Google Scholar]
  12. Ghadially F. N., Mehta P. N. Ultrastructure of osteogenic sarcoma. Cancer. 1970 Jun;25(6):1457–1467. doi: 10.1002/1097-0142(197006)25:6<1457::aid-cncr2820250626>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  13. Nakagawa M., Urist M. R. Chondrogenesis in tissue cultures of muscle under the influence of a diffusible component of bone matrix. Proc Soc Exp Biol Med. 1977 Apr;154(4):568–572. doi: 10.3181/00379727-154-39720. [DOI] [PubMed] [Google Scholar]
  14. Nakakuki K., Shimokawa K., Yamauchi H., Ojima A. A spontaneous transplantable osteogenic sarcoma in AKR/Ms mice. Gan. 1976 Aug;67(4):513–521. [PubMed] [Google Scholar]
  15. Nogami H., Urist M. R. Substrata prepared from bone matrix for chondrogenesis in tissue culture. J Cell Biol. 1974 Aug;62(2):510–519. doi: 10.1083/jcb.62.2.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peterkofsky B., Diegelmann R. Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry. 1971 Mar 16;10(6):988–994. doi: 10.1021/bi00782a009. [DOI] [PubMed] [Google Scholar]
  17. SUGIURA K., STOCK C. C. Studies in a tumor spectrum. I. Comparison of the action of methylbis (2-chloroethyl)amine and 3-bis(2-chloroethyl)aminomethyl-4-methoxymethyl -5-hydroxy-6-methylpyridine on the growth of a variety of mouse and rat tumors. Cancer. 1952 Mar;5(2):382–402. doi: 10.1002/1097-0142(195203)5:2<382::aid-cncr2820050229>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  18. Terashima Y., Urist M. R. Differentiation of cartilage from calvarial bone under the influence of bone matrix gelatin in vitro. Clin Orthop Relat Res. 1975 Nov-Dec;(113):168–177. doi: 10.1097/00003086-197511000-00027. [DOI] [PubMed] [Google Scholar]
  19. Urist M. R. A bone morphogenetic system in residues of bone matrix in the mouse. Clin Orthop Relat Res. 1973 Mar-Apr;(91):210–220. doi: 10.1097/00003086-197303000-00029. [DOI] [PubMed] [Google Scholar]
  20. Urist M. R., Granstein R., Nogami H., Svenson L., Murphy R. Transmembrane bone morphogenesis across multiple-walled diffusion chambers. New evidence for a diffusible bone morphogenetic property. Arch Surg. 1977 May;112(5):612–619. doi: 10.1001/archsurg.1977.01370050072012. [DOI] [PubMed] [Google Scholar]
  21. Urist M. R., Iwata H., Ceccotti P. L., Dorfman R. L., Boyd S. D., McDowell R. M., Chien C. Bone morphogenesis in implants of insoluble bone gelatin. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3511–3515. doi: 10.1073/pnas.70.12.3511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Urist M. R., Nakata N., Felser J. M., Nogami H., Hanamura H., Miki T., Finerman G. A. An osteosarcoma cell and matrix retained morphogen for normal bone formation. Clin Orthop Relat Res. 1977 May;(124):251–266. [PubMed] [Google Scholar]
  23. Wilby O. K., Ede D. A. A model generating the pattern of cartilage skeletal elements in the embryonic chick limb. J Theor Biol. 1975 Jul;52(1):199–217. doi: 10.1016/0022-5193(75)90051-x. [DOI] [PubMed] [Google Scholar]

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