Human amniotic tumor that induces new bone formation in vivo produces growth-regulatory activity in vitro for osteoblasts identified as an extended form of basic fibroblast growth factor.
Tumors occasionally stimulate bone formation and cause osteoblastic metastases. Although this occurs most frequently in widespread prostate cancer, human prostate cancer cells are difficult to grow in culture without changing their phenotype, and the few available prostatic cancer lines do not increase bone formation in vivo. To identify tumor-derived osteoblast-stimulatory factors, we studied a long-established human tumor cell line derived from human amnion that has, in the past, been reported to cause bone formation in vivo when inoculated into nude mice. Tumor cells were inoculated into nude mice and induced extensive new bone formation. To characterize osteoblast growth factors produced by these tumor cells, solid tumor was isolated from the mice and extracted at neutral pH. Biological activity, assessed by stimulation of proliferation of MG-63 osteoblast-like cells, was used to monitor purification after heparin-Sepharose column chromatography, Mono-S, and C4 reverse-phase high-performance liquid chromatography. An extend amino-terminal form of basic fibroblast growth factor (FGF) was purified by its capacity to stimulate proliferation in MG-63 cells and partially sequenced. Basic FGF is also known to stimulate proliferation in MG-63 cells and other osteoblasts in vitro and bone formation in vivo. In summary, these human tumor cells stimulate new bone formation in vivo and produce an osteoblast stimulating activity in vitro, which has been identified as a form of basic FGF.
Izbicka
E
E
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877, USA.
Dunstan
C
C
Esparza
J
J
Jacobs
C
C
Sabatini
M
M
Mundy
G R
GR
D000595:Amino Acid Sequence; D000650:Amnion / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D016222:Fibroblast Growth Factor 2