Osteosarcomas contain variable amounts of bony tissue, but the mechanism of bone formation by osteosarcoma is not well understood. While a number of cultured human osteosarcoma cell lines have been established, they are maintained by different media and differ qualitatively with regard to bone formation. We examined different media for their ability to support bone formation in vitro and found that alpha-modification of Eagle's minimal essential medium supplemented with beta glycerophosphate was best for this purpose, because it contained the proper calcium and phosphate concentrations. Subsequently, we compared seven human osteosarcoma cell lines under the same experimental conditions to clarify their ability to induce bone formation. NOS-1 cells most frequently exhibited features of bone formation in vitro and in nude mice. Collagen synthesis by tumour cells themselves seemed to be the most important factor for bone volume. However, even HuO9 cells, which lacked collagen synthesis and failed to form bone in vitro, successfully formed tumours containing bone in nude mice. Histological analysis of HuO9 cells in diffusion chambers implanted in nude mice and the findings of polymerase chain reaction indicated that the phenomenon was probably due to bone morphogenetic protein.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Bentley H, Handy FC, Hart KA, Seid JM, Williams J, Johnstone D, Russell RGG (1992) Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. Br J Cancer 66: 1159–1163
Bingham PJ, Raisz LG (1974) Bone growth in organ culture: effect of phosphate and other nutrients on bone and cartilage. Calcif Tissue Res 14: 31–48
Boden SD, Soyoola E, Nanes M, Titus FL, Rubin JE, Catherwood BD (1993) Mineralization by β-glycerophosphate enhances osteocalcin production by MC3T3-E1 cells in α-MEM but not BGJb. J Bone Miner Res 8 [Suppl]: 297–297
Chung C-H, Golub EE, Forbes E, Tokuoka T, Shapiro IM (1992) Mechanism of action of β-glycerophosphate on bone cell mineralization. Calcif Tissue Int 51: 305–311
Collin P, Nefussi JR, Wetterwald A, Nicolas V, Boy-Lefevre M-L, Fleisch H, Forest N (1993) Expression of collagen, osteocalcin, and bone alkaline phosphatase in a mineralizing rat osteoblastic cell culture. Calcif Tissue Int 50: 175–183
Franceshi RT, Iyer BS (1992) Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells. J Bone Miner Res 7: 235–246
Hammond RG, Schwall R, Dudley A, Berkemeier L, Lai C, Lee J, Cunningham N, Reddi AH, Wood WI, Mason AJ (1991) Bone-inducing activity of mature BMP2b produced form a hybrid BMP2a/2b precursor. Mol Endocrinol 5: 149–155
Hotta T, Motoyama T, Watanabe H (1992) Three human osteosarcoma cell lines exhibiting different phenotypic expressions. Acta Pathol Jpn 42: 595–603
Kawai A (1990) A newly established human osteosarcoma cell line with osteoblastic properties. Clin Orthop 259: 256–267
Kivirikko KI, Laitien O, Prockop DJ (1967) Modification of a specific assay for hydroxyproline in urine. Anal Chem 19: 249–255
Motoyama T, Hojo H, Watanabe H (1986) Comparison of seven cell lines derived from human gastric carcinomas. Acta Pathol Jpn 36: 65–83
Pitaru S, Kotev-Emeth S, Noff D, Kaffuler S, Savion N (1993) Effect of fibroblastic growth factor on the differentiation of adult stromal bone marrow cells: enhanced development of mineralized bone-like tissue in culture. J Bone Miner Res 8: 919–929
Rodan SB, Imai Y, Thied A, Wesolowski G, Bar-Shavit Z, Shull S, Mann K, Rodan GA (1987) Characterization of a human osteosarcoma cell line (Saos-2) with osteoblastic properties. Cancer Res 47: 4961–4966
Sandberg M, Aro HT, Vuorio E (1993) Gene expression during bone repair. Clin Orthop 289: 292–312
Sekiguchi M, Asanuma K, Satomura T, Fukusima H, Fujji T, Shimoda T, Fukunaga M, Ishikawa E (1983) A cultured cell line established in vitro from human osteosarcoma. Jpn J Exp Med 53: 289–292
Sudo H, Kodama H, Amagai Y, Yamamoto S, Kasai S (1983) In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol 96: 191–198
Takaoka K, Yosikawa H, Masuhara K, Sugamoto, K, Tsuda T, Aoki Y, Ono K, Sakamoto Y (1989) Establishment of a cell line producing bone morphogenetic protein from a human osteosarcoma. Clin Orthop 244: 258–264
Tenenbaum HC, Hersche, JNM (1982) Differentiation of osteoblasts and formation of mineralized bone in vitro. Calcif Tissue Int 34: 76–79
Tsuchiya H, Morisita H, Tomita K, Ueda Y, Tanaka M (1993) Differentiating and antitumor activities of 1α,25 dihydroxyvitamin D3 in vitro and 1α-hydroxyvitamin D3 in vivo on human osteosarcoma. J Orthop Res 11: 122–130
Tureck SM (1984) Physiology and mineralization of bone. In: Tureck SM (ed) Orthopedics. Principles and application, 4th edn, vol 1. Lippincott, Philadelphia, pp 136–190
Wang E, Rosen V, d'Alessandro JS, Baudy M, Cordes P, Harada T, Israel. DI, Hewick RM, Kerns KM, Lapan P, Luxenberg DP, McQuaid D, Moutsatsos IK, Nove J, Wozney JM (1990) Replacement human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 87: 2220–2224
Whitson SW, Whiston MA, Bowers DE Jr, Fal, MC (1992) Factors influencing synthesis and mineralization of bone matrix from fetal bovine cells in vitro. J Bone Miner Res 7: 727–741
Yamane T (1985) Establishment and characterization of cell lines derived from a human osteosarcoma. Clin Orthop 199: 261–271
About this article
Cite this article
Ogose, A., Motoyama, T., Watanabe, H. et al. Bone formation in vitro and in nude mice by human osteosarcoma cells. Vichows Archiv A Pathol Anat 426, 117–125 (1995). https://doi.org/10.1007/BF00192632
- Cell line
- Alkaline phosphatase
- Bone morphogenetic protein