UMLS:C0029463 - FACTA Search

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Query: UMLS:C0029463 (osteosarcoma)
16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PA-III rat prostate adenocarcinoma cells are capable of inducing osteoblastic reaction after inoculation onto rat skeleton. In this study PA-III cells and osteoblast-derived rat osteosarcoma cells (UMR 106 cells) were employed to characterize the cellular interactions in the PA-III cell-induced bone tumors, in vitro. Insulin-like growth factor-I (IGF-I) and conditioned media (CM) of UMR 106 cells stimlated tritiated-thymidine incorporation into the DNA of PA-III cells growing in serum-free media. This effect was inhibited by monoclonal anti-hIGF-I antibody. In addition PA-III cell CM contained proteinolytic activity for the IGF-binding proteins of UMR 106 cell CM (IGFBP-1 and -2). This proteinase activity hydrolyzed also benzyloxycarbonyl-lysine thiobenzyl ester (BLT) and its action on IGFBPs and BLT was inhibited by benzamidine and aprotinin. Proteinase activity of PA-III cell CM when bound covalently to tritiated-dilsopropylfluoro-phosphate (DFP) and then analyzed on SDS-PAGE gel electrophoresis, revealed the presence of radioactivity linked with a 35 kDa protein band. This proteinase was eluted in the void volume of the G-50 sephadex column and was retained on and eluted from p-benzamidine affinity column. The 35 kDa proteinase was retained on and was eluted from cartridges of the C18 silica by 80% acetonitrile over 0.1% trifuroacetic acid. This partially purified material hydrolyzed BLT substrate and IGFBPs of UMR 106 cell CM and its effect was inhibited by benzamidine and aprotinin. These data indicate that PA-III cell CM contains a 35 kDa proteinase capable of digesting the IGFBPs and thus increases the bioavailability of osteoblast-derived IGFs. This mechanism may participate in the pathophysiology of the PA-III cell-induced bone tumor and its subsequent osteoblastic reaction.
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PMID:Proteinolytic activity against IGF-binding proteins involved in the paracrine interactions between prostate adenocarcinoma cells and osteoblasts. 137 96

Insulin-like growth factor-I (IGF-I) is a potent stimulator of bone formation. Whether this growth factor also induces bone resorption has not been studied in detail. We used two organ culture systems to examine the direct effect of IGF-I on bone resorption. Fetal mouse radii/ulnae, containing mature osteoclasts, showed no response to IGF-I, indicating that osteoclastic activity is not influenced by IGF-I. Fetal mouse metacarpals/metatarsals, containing just osteoclast precursors and progenitors, showed an increase in resorption in response to IGF-I, indicating that IGF-I stimulates the formulation of osteoclast precursors/progenitors and thereby increases the number of osteoclasts. Interleukin-6 (IL-6) has been hypothesized to be a mediator of bone resorptive agents such as parathyroid hormone (PTH). Both radii/ulnae and metacarpals/metatarsals reacted to IGF-I with an increase in IL-6 production. IL-6 production by UMR-106 osteogenic osteosarcoma cells was positively modulated by IGF-I, indicating that osteoblasts are likely to be the cells responsible for increased IL-6 production by the bones, and that IL-6 might be a mediatory of IGF-I-stimulated bone resorption.
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PMID:Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I. 156 29

Although a small number of estrogen receptors (ER) were visualized in osteoblastic cells, and estradiol (E2) has some effects on osteoblasts in vitro, the direct action of E2 on osteoblasts has not been fully established. To determine the presence of functional ER in osteoblasts, we transfected cells with a plasmid containing the chloramphenicol acetyl transferase (CAT) reporter gene and the estrogen-responsive element (ERE) from the vitellogenin A2 gene. E2-dependent induction of CAT activity was determined 48 h after transient transfection and subsequent treatment with 10-100 nM 17 beta-E2. 17 beta-E2, but not 17 alpha-E2, dihydrotestosterone, or progesterone, induced CAT activity in a dose-dependent manner (up to 6-fold) in rat calvarial fraction-3, RCT-3, PyMS, and UMR-106 cells as well as in the human osteosarcoma cell line SaOS-2/B-10. In contrast, E2 had no effect on the induction of CAT activity in the preosteoblastic cell lines RCT-1 and TRAB-11, in the rat osteosarcoma cell line ROS 17/2.8, and in the fibroblastic cell lines BALB-c/3T3 and NRK. Over-expression of ER using a simian virus-40-based expression vector not only conferred or enhanced E2-dependent induction of CAT in all cell types, but augmented E2-dependent expression of insulin-like growth factor-I and E2-stimulated DNA synthesis in primary calvarial and PyMS osteoblastic cells, respectively. These data show the presence of low levels of functional endogenous ER in some, but not all, osteoblastic cells and suggest that the abundance of ER may be rate limiting in the action of E2 on these cells.
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PMID:Functional estrogen receptors in osteoblastic cells demonstrated by transfection with a reporter gene containing an estrogen response element. 177 66

These studies were undertaken to characterize the physiological fate of the insulin-like growth factor-I (IGF-I)-type I receptor complex in MG-63, an IGF-responsive human osteosarcoma cell line. To investigate this, a photoreactive iodinated derivative of IGF-I [5-azido-2-nitrobenzoyl-125I-IGF-I (ANBz-125I-IGF-I)] was synthesized. This derivative retained biological activity and photolabeled a cell surface component on MG-63 cells with the size and binding specificity characteristic of the type I IGF receptor. To assess the stability of the photoaffinity-labeled IGF-I receptor complex, quiescent monolayers of MG-63 cells were incubated with ANBz-125I-IGF-I at 2 C, photolyzed, and then warmed to 37 C. At various times the monolayers were solubilized and the receptor complex was identified by quantitative autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under these conditions the photoaffinity-labeled IGF-I receptor complex was relatively stable, with a half-life of 11 +/- 2 h in five experiments. To determine if the complex undergoes internalization, its susceptibility to hydrolysis by trypsin at 2 C was measured. When cells that were labeled at 2 C were warmed to 37 C, a trypsin-insensitive band appeared within 20 min, reached a maximum by 1 h, and declined thereafter; however, an average of only 7% (5-8% in four experiments) of the total labeled receptor pool was present intracellularly at 1 h, and this declined to less than 1% by 4 h. A similar distribution of receptors was observed in cells photolabeled after incubation with ANBz-125I-IGF-I at 37 C, indicating that this distribution was not the result of altered metabolism of the photolabeled receptor complex. Lysosomotropic agents inhibited degradation of the complex, but did not alter its distribution between the cell surface and interior. These results indicated that the IGF-I-type I receptor complex is relatively stable and does not undergo rapid ligand-induced down-regulation and degradation. These observations suggest a model in which the IGF-receptor complex functions while present at or near the cell surface.
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PMID:Metabolism of photoaffinity-labeled insulin-like growth factor-I receptors by human cells in vitro. 215 97

Low-level exposure to lead impairs longitudinal growth in children and in experimental animals. The proposed mechanisms include decreased osteocalcin secretion in response to 1 alpha,25-(OH)2 vitamin D3 and decreased response to insulin-like growth factor-I. The interaction of lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I was investigated in an osteoblast-like cell line from rat osteosarcoma, ROS 17/2.8. Cells were cultured 24 hr in a serum-free medium with lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I. 1 alpha,25-(OH)2 vitamin D3 (10 nM) evoked a 4-5 X increase in osteocalcin secretion and a 100% increase in cellular alkaline phosphatase activity but no increase in DNA/cell layer. Insulin-like growth factor-I (92.5 ng/ml) evoked a 100% increase of osteocalcin secretion and a 20% increase in cellular DNA contents but no change in cellular alkaline phosphatase activity. Basal and stimulated cellular osteocalcin secretion, cellular alkaline phosphatase activity, and DNA contents were significantly inhibited by addition of 1-10 microM lead. The data are consistent with a toxic effect of lead on osteoblastic function and the cellular responses to 1 alpha,25-(OH)2 vitamin D3 and insulin-like growth factor-I. This interaction may be relevant to impaired childhood growth at low levels of lead exposure.
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PMID:Lead inhibits the basal and stimulated responses of a rat osteoblast-like cell line ROS 17/2.8 to 1 alpha,25-dihydroxyvitamin D3 and IGF-I. 233 May 89

Insulin-like growth factor-II is known to stimulate the proliferation and differentiation of osteoblasts in part through activation of the type-2 insulin-like growth factor receptor. The present study examined the type-2 insulin-like growth factor receptors of three normal osteoblast-like cells and three osteosarcoma-derived osteoblast-like cells (OGA, SU, and IMAI) from humans. [125I]insulin-like growth factor-II was used for the binding studies. All of the cell types had high affinity binding sites for insulin-like growth factor-II (dissociation constants [Kd] < or = 1 nM). The concentration of these sites was 10 to 24-fold higher in normal osteoblasts than in the osteosarcoma cells studied. Unlabeled insulin-like growth factor-II inhibited the binding of [125I]insulin-like growth factor-II to the cells in a dose-dependent manner; however, unlabeled insulin-like growth factor-I and insulin were less effective. Covalent crosslinking of insulin-like growth factor-II binding sites gave molecular mass estimates of M(r) 250,000 in human osteoblast cells, 250,000 and 130,000 in OGA cells, 240,000 in SU cells, and 250,000 and 130,000 in IMAI cells. Unlabeled insulin-like growth factor-II inhibited all affinity labeling. In Northern blot analysis, the type-2 insulin-like growth factor receptor mRNA of normal osteoblasts was seen in greater abundance than it was in osteosarcoma cells. These results indicate that the numbers of type-2 insulin-like growth factor receptors differ between normal and transformed osteoblasts and that the differential expression of the receptor may be due to the differentiation of osteoblasts.
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PMID:Comparison of the type-2 insulin-like growth factor receptor in normal osteoblasts and osteosarcoma-derived osteoblast-like cells. 747 41

A pertussis toxin-sensitive G protein has been reported to play a role in the mitogenic response to insulin-like growth factor-I (IGF-I) in mouse fibroblasts, and diacylglycerol generation has been shown to accompany growth stimulation by IGF-I of several cell lines. We have examined the roles of pertussis toxin sensitive G proteins and diacylglycerol generation in signaling by the insulin-like growth factor-I receptor in a cell line that is very responsive to IGF-I, the human osteosarcoma cell line, MG-63. Pertussis toxin failed to inhibit IGF-I induced [3H]-thymidine incorporation into DNA. Furthermore, the stable analog GTP gamma S had no effect on the binding of 125I-labelled IGF-I to MG-63 membrane preparations. Following addition of IGF-I to growth-arrested MG-63 cells there was no increase in diacylglycerol levels over 30 min. We conclude that the activated IGF-I receptor does not use pertussis toxin sensitive G proteins or diacylglycerol generation in a pathway leading to DNA synthesis in MG-63 cells.
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PMID:Evidence against roles for pertussis toxin sensitive G proteins or diacylglycerol generation in insulin-like growth factor-1 stimulated DNA synthesis in MG-63 osteosarcoma cells. 782 13

Insulin-like growth factor-I (IGF-I) and IGF-II have powerful, well defined effects on osteoblastic cells, stimulating their proliferation and inducing collagen synthesis, but the role of IGF-I and -II in modulating osteoclast differentiation and activity remains unclear. We first examined the bone-resorptive effects of IGF-I and IGF-II by assessing 45Ca2+ release from neonatal mouse calvarial bones. Both IGFs dose dependently stimulated bone resorption, with an EC50 of 8 x 10(-9) M for IGF-I and 2 x 10(-8) M for IGF-II. We then tested the effects of the IGFs on bone resorption by rat isolated osteoclasts cultured on ivory slices. Neither IGF-I nor IGF-II stimulated isolated osteoclast activity. However, in the presence of either primary mouse osteoblasts or human osteosarcoma MG 63 cells, both IGFs enhanced osteoclast resorptive activity, with an EC50 of 5 x 10(-10) M for IGF-I and 10(-9) M for IGF-II. Stimulation was not mediated by BALB/c/3T3 cells, a nonosteoblastic cell line. The effects of the IGFs were blocked by alpha IR-3, an antibody to the type I IGF receptor, but not by beta-galactosidase, a lysosomal enzyme that competes with IGF-II for the type II IGF receptor. We then examined the effects of the IGFs on the formation of osteoclast-like multinucleate cells (MNCs) in mouse bone marrow cultures. IGF-I and -II dose dependently increased the number of tartrate-resistant acid phosphatase (TRAP)-positive MNCs, although their effects were less than that of 1,25-dihydroxyvitamin D3 (a hormone that induces osteoclast differentiation). No TRAP-positive MNCs appeared in the absence of these hormones. Like authentic osteoclasts, the TRAP-positive MNCs formed in response to IGF-I and -II bound [125I]salmon calcitonin. When mouse bone marrow cells were cultured on ivory slices in the presence of either IGF-I or IGF-II for 10 days, numerous resorption lacunae were formed. beta-Galactosidase had no effect on IGF-mediated osteoclast formation. These results are strong evidence that both IGF-I and IGF-II stimulate bone resorption in vitro by enhancing osteoclast formation and function. Our data also suggest that the IGFs act through the intermediary of osteoblastic cells to stimulate osteoclast activity and that the type I, but not the type II, IGF receptor is involved in their responses. We propose that the local production of IGF-I and IGF-II may modulate both osteoblast-osteoclast interactions and osteoclast formation and play an important role in bone remodeling.
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PMID:Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclast formation and function. 782 21

Insulin-like growth factor-I (IGF-I) has been reported to mediate the effects of oestradiol-17 beta in the osteoblast-like osteosarcoma cell line ROS 17/2.8 and to stimulate directly cell proliferation in cell cultures derived from rat calvaria. Few data are available on the role of IGF-I in androgen stimulation of cultured skeletal cells and in oestrogen and androgen stimulation of bone and cartilage in vivo. The purpose of the present study was to compare the effect of IGF-I in rats in vivo with its effect in vitro on calvarial bone cells from females (responding only to oestrogens) and from males (responding only to androgens, such as testosterone and dihydrotestosterone). We found that IGF-I stimulated, in a dose- and time-dependent manner, the specific activity of creatine kinase (CK, a marker of skeletal cell division), in both female and male calvarial bone cells, in ROS 17/2.8 cells and in epiphyseal cartilage cell cultures. Maximal stimulation occurred at 30 or 100 nM within 1-2 h after stimulation. In ROS 17/2.8 cells, IGF-I stimulated [3H]thymidine incorporation, after 22 h of treatment, in parallel with CK activity. IGF-II, at higher doses than IGF-I (maximal stimulation at 300 nM), stimulated CK specific activity in female- and male-derived calvarial cell cultures. When IGF-I (50 nM) was applied together with oestradiol-17 beta (30 nM) or with dihydrotestosterone (300 nM) there was no additional response in the cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation by insulin-like growth factor-I of creatine kinase activity in skeletal-derived cells and tissues of male and female rats. 782 90

Insulin-like growth factors are abnormally expressed in some pediatric solid tumors. In addition, tumors that do not show significant alterations in pattern of expression are responsive to and may be dependent upon insulin-like growth factors for proliferation. These can be produced by the tumor cells (autocrine), surrounding stromal cells (paracrine), or at a distance (endocrine). Insulin-like growth factor-II plays a role in Wilm's tumor, neuroblastoma, and rhabdomyosarcoma, either as a proliferation factor, a motility factor, or both. Insulin-like growth factor-I may regulate osteosarcoma and the Ewing's family of tumors (primitive neuroectodermal tumors). Understanding the biology of these growth factors and their receptors can lead to new therapeutic approaches.
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PMID:Diverse roles of insulin-like growth factors in pediatric solid tumors. 805 16

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