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

We studied the expression of the members of the beta 1 integrin family and extracellular matrix ligands in osteosarcoma tissues. Immunostaining of primary osteosarcomas with use of specific antibodies for alpha 1-alpha 6 integrin subunits, fibronectin, type-I collagen, and laminin gave characteristic patterns: despite the diffuse expression of type-I collagen in all 16 osteosarcomas, collagen receptors were detected in only one. Laminin and laminin receptors were expressed poorly. In contrast, the alpha 4 and alpha 5 fibronectin receptors were found in 100 and 75%, respectively, which correlates very well with the strong expression of fibronectin in the stroma. The other ligand for alpha 4, vascular cell adhesion molecule-1, was not expressed in the seven specimens tested. Therefore, primary osteosarcomas closely interact with fibronectin through alpha 4 and possibly alpha 5 subunits of the beta 1 integrin. We also examined the expression of integrins in six metastatic foci in five patients. Some change for the expression was detected in all six specimens, however, the change varied. In contrast, osteosarcoma cells obtained from invasive portions of tumors exhibited new and augmented expression of certain integrins in two of the three cases in which their ligands were also expressed.
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PMID:Distribution of integrins and their matrix ligands in osteogenic sarcomas. 832 45

We investigated the effects of dibutyryl cyclic adenosine 3',5'-monophosphate (Bt2cAMP) on the differentiation of Dunn osteosarcoma cells. Flow-cytometric analysis and DNA synthesis assay showed that Bt2cAMP decreased the cell population in the S phase in a time- and dose-dependent manner. Also, the cells showed distinct morphological and functional alterations; the cell morphology changed to a fibroblast-like appearance with long and thin protoplasmic processes, the knobs or blebs on both the cell membrane and nuclear membrane disappeared and the intracellular alkaline phosphatase activity increased. Moreover, Bt2cAMP-treated cells secreted a large quantity of fibronectin, which was deposited on the extended cell surface in the culture medium. Thus, Dunn osteosarcoma cells are differentiated morphologically and functionally by Bt2cAMP, and might be transformed to benign precursor cells.
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PMID:Differentiation of Dunn osteosarcoma cells in response to dibutyryl cyclic 3',5'-adenosine monophosphate. 838 87

Components of the extracellular matrices (ECM) exert pleiotropic effects in many cell systems, but little is known of the effect of ECM on hormone signal transduction. We have investigated the effect of ECM substrates on cell growth and signal transduction by calcitonin (CT) and parathyroid hormone (PTH) using the rat osteosarcoma cell line, UMR 106-06. Type I collagen (collagen[I]) and Matrigel changed the morphology of the cells and significantly inhibited cell growth by 37% or 23%, respectively, compared with control. None of laminin, fibronectin, or type IV collagen affected cell shape or proliferation. Cells cultured on collagen (I)-coated plates showed increased specific binding of labeled CT compared with cells on plastic plates. The effect was apparent by 24 h and persisted for at least 72 h. None of the other ECM affected CT binding. Scatchard analysis revealed that collagen(I) increased CT receptor numbers but not receptor affinity. Consistent with increased binding capacity, cells plated on collagen(I) had increased responses to each of CT and PTH in terms of cyclic adenosine monophosphate (cAMP) production compared to control cells. In addition, cAMP production by prostaglandin E2, cholera toxin, and forskolin was increased by 30-70% compared to control. These data suggest that collagen(I) had effects not only on membrane receptors but on guanosine triphosphate (GTP) binding proteins (G proteins). The effect of collagen(I) on CT binding was no longer present when the cells were freed from the plates by enzymatic dispersion and binding measured in cell suspensions. In UMR 106-01 cells transiently transfected with the porcine CT receptor cDNA, binding was similarly induced by collagen(I). These data are the first demonstration that collagen(I) may play an important role in signal transduction, affecting both receptors and G proteins in UMR 106-06 cells. These results draw attention to the potential role of the ECM of bone in hormone-induced responses.
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PMID:Type I collagen substrate increases calcitonin and parathyroid hormone receptor-mediated signal transduction in UMR 106-06 osteoblast-like cells. 839 Oct 4

Proteolysis triggered by receptor-bound urokinase-type plasminogen activator (uPA) involves a cascade of species-specific molecular interactions. To study the role of the uPA receptor (uPAR) in such interactions, a human osteosarcoma cell line (HOS), which normally expresses low levels of uPAR, was transfected with human uPAR complementary DNA. One of several stably transformed clonal cells lines, designated 2A2, was characterized and compared to the parental HOS, revealing the following: (a) stable incorporation of uPAR complementary DNA into the genome demonstrated by Southern blot analysis; (b) a 10-fold increase in steady state mRNA levels of uPAR assessed by Northern blot analysis; (c) a 2-fold increase in the surface expression of glycosylphosphatidylinositol anchored uPAR protein determined by enzyme-linked immunosorbent assay and by the specific binding of radiolabeled single chain uPA; (d) a 2-fold increase in internalization and degradation of radiolabeled uPA/PAI-1 complexes; and (e) a 2-fold increase in receptor-bound uPA-mediated plasmin generation measured by the cleavage of a chromogenic substrate and degradation of 125I-labeled laminin. The involvement of uPAR in cellular processes was determined by comparing 2A2 and HOS cells in in vitro migration and invasion assays. The migration of 2A2 cells were slower on fibronectin-coated surfaces in a linear under-agarose assay, but both cell lines migrated at the same rate on uncoated polycarbonate filters in Boyden chamber assays. In the invasion experiments, 4 times more 2A2 than HOS cells penetrated through the barrier of reconstituted basement membrane Matrigel. These data suggest that uPAR does not potentiate random cell migration but facilitates matrix degradation and subsequent cell invasion.
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PMID:Overexpression of urokinase receptor increases matrix invasion without altering cell migration in a human osteosarcoma cell line. 839 87

Two sets of clonal cell populations differing in the expression of osteoblastic traits, the rat osteosarcoma cell lines ROS 17/2.8 and ROS 25/1 and the immortalized fetal rat calvarial cell lines RCT-1 and RCT-3, were compared for their ability to attach to a series of extracellular matrix (ECM) constituents in vitro. Both osteoblastic (ROS 17/2.8, RCT-3) and nonosteoblastic (ROS 25/1, RCT-1) cell lines attached in a time- and concentration-dependent manner to plates coated with fibronectin (FN), osteopontin (OP), type I collagen (Col I), type IV collagen (Col IV), and laminin (LN) but only weakly to osteocalcin (OC) and thrombospondin (TSP). In both systems, the osteoblastic and nonosteoblastic clones attached identically to FN. Both ROS 17/2.8 and ROS 25/1 attached to similar molar amounts of substrate with the same preference order: FN > LN > Col I > or = Col IV. Maximal ROS 17/2.8 attachment to OP was > or = Col I but required approximately 2.5 times more substrate. ROS 25/1 attached less effectively than ROS 17/2.8 to most non-FN substrates. RCT-3 cells attached similarly to ROS 17/2.8 except that the preference order for Col I and LN was reversed and attachment to OP was lower than for ROS 17/2.8 RCT-1 cells attached best to Col I rather than FN, and equaled or surpassed RCT-3 in attachment to other non-FN substrates. Thus in these experimental systems, cells expressing an osteoblast-like phenotype exhibited generally similar ECM attachment properties. Their nonosteoblastic counterparts recognized the same spectrum of ECM constituents but differed from the osteoblastic cells and from each other in the effectiveness of their attachment to substrates other than FN.
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PMID:Attachment to extracellular matrix molecules by cells differing in the expression of osteoblastic traits. 845 84

Fibronectin (FN) is an important adhesive noncollagenous glycoprotein involved in maintenance of the extracellular matrix and cell adhesiveness, loss of which has been implicated in the metastatic potential of cells. Regulation of FN occurs at the transcriptional level by the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Transient transfection of homologous and heterologous promoter reporter constructs into ROS 17/2.8 (rat osteosarcoma), NIH 3T3 (mouse fibroblast), and MCF-7 (human mammary carcinoma) cell lines showed a consistent two- to threefold induction of transcription when stimulated with 1,25-(OH)2D3. These heterologous promoter transfection studies with gel shift analysis locate a third, natural DR6-type vitamin D responsive element (VDRE) at nucleotide positions -171 to -154 in the murine FN promoter. Interestingly, this VDRE is also present in rat and human FN promoters. This study shows that 1,25-(OH)2D3 induces FN transcription from an existing elevated basal transcriptional activity by acting through two putative hexameric core binding motifs which bind VDR homodimers. Furthermore, the FN VDRE is the first homodimer-type VDRE that is not overlaid by a DR3-type structure.
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PMID:Identification of a vitamin D3 response element in the fibronectin gene that is bound by a vitamin D3 receptor homodimer. 886 8

Metastasis accounts for most deaths in cancer patients. Tumor cell adhesion to the extracellular matrix through integrins is thought to be a critical step in metastasis and a potential target for therapeutic intervention. We show here that treatment of human osteosarcoma, melanoma and carcinoma cells with a polymeric form of fibronectin (sFN), before inoculation into nude mice, prevented tumor formation. Intraperitoneally administered sFN significantly reduced lung colonization from intravenously injected tumor cells (experimental metastasis) and from subcutaneous tumors in nude mice (spontaneous metastasis). Treatment with sFN blocked cell spreading and migration in vitro suggesting a possible mechanism for the antimetastatic effect.
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PMID:A polymeric form of fibronectin has antimetastatic effects against multiple tumor types. 889 45

A midregion fragment of PTH-related protein (PTHrP), which is intensively conserved across species, has been identified as a secretory product of several different cell types, including keratinocytes and squamous carcinomas. As recent data suggest that a midregion PTHrP fragment may be biologically active, we hypothesized that midregion PTHrPs interact with unique cell surface receptors that mediate autocrine or paracrine action. Dose-dependent transient elevations in intracellular calcium ([Ca2-]i) were observed in fura-2-loaded SqCC/Y1 squamous carcinoma cells exposed to human (h) PTHrP-(67-86)NH2, [Tyr36]hPTHrP-(1-36)NH2, and hPTHrP-(1-141) at concentrations ranging from 1 pM to 1 microM. The effects of maximal stimulatory concentrations of [Tyr36]PTHrP-(1-36)NH2 and PTHrP-(67-86)NH2 on [Ca2+]i were additive. The inhibitory PTH analog, [D-Trp12,Tyr34]bovine PTH-(7-34)NH2, attenuated the [Ca2+]i response to [Tyr36]hPTHrP-(1-36)NH2, but not that to PTHrP-(67-86)NH2. These data suggest that PTHrP-(67-86)NH2 activates a different receptor pathway in SqCC/Y1 cells from the one activated by [Tyr36]hPTHrP-(1-36)NH2. Radiolabeled PTHrP-(67-86)NH2 did not bind to SqCC/Y1 cells, and PTHrP-(67-86)NH2 did not compete for binding of 125I-labeled [Tyr36]PTHrP-(1-36)NH2 to PTH/PTHrP receptors on SaOS-2 osteosarcoma cells. Activation of the phospholipase C pathway by PTHrP-(67-86)NH2 was confirmed by exposing SqCC/Y1 cells to peptide for 1 min and measuring the accumulation of inositol trisphosphates. PTHrP-(67-86)NH2 treatment (100 nM) resulted in maximal stimulation of inositol trisphosphates of 3.1 +/- 0.1-fold over the control value, with an EC50 of 1.5 +/- 1.2 nm. In contrast, PTHrP-(67-86)NH2 (0.1 nM to 1 microM) did not stimulate adenylyl cyclase in SqCC/Y1 cells despite vigorous stimulation of cAMP formation by isoproterenol (1 microM) to 66-fold over the basal value. To determine whether messenger RNA (mRNA) prepared from SqCC/Y1 cells would direct the translation of a receptor protein that mediated a [Ca2+]i response to PTHrP-(67-86)NH2, we performed expression studies in Xenopus oocytes. Fluo-3 fluorescence in Xenopus oocytes expressing SqCC/Y1 mRNA was visualized by confocal video microscopy after exposure to 1 microM PTHrP-(67-86)NH2. Clear increases in [Ca2+]i were detected in mRNA-injected, but not in sham-injected, oocytes. Finally, we examined the effect of PTHrP-(67-86)NH2 treatment on fibronectin secretion from SqCC/YN1 cells. A significant 3.5-fold increase in fibronectin secretion into conditioned medium was observed when SqCC/Y1 cells were exposed to 100 nM PTHrP-(67-86)NH2, and this effect was dose dependent, with an EC50 of 0.1 nM. We conclude that PTHrP-(67-86)NH2 activates phospholipase C-dependent pathways in SqCC/Y1 cells through a receptor distinct from that activated by PTHrP-(1-36) in the same cells. As a midregion secretory fragment of PTHrP has been partially purified from several different cell types, this receptor may have broad biological significance.
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PMID:A midregion parathyroid hormone-related peptide mobilizes cytosolic calcium and stimulates formation of inositol trisphosphate in a squamous carcinoma cell line. 894 Mar 60

Two forms of the transmembrane human protein tyrosine phosphatase (PTP sigma), generated by alternative splicing, were identified by cDNA cloning and Northern hybridization with selective cDNA probes. The larger form of PTP sigma is expressed in various human tissues, human osteosarcoma, and rat tibia. The hPTP sigma cDNA codes for a protein of 1911 amino acid residues and is composed of a cytoplasmic region with two PTP domains and an extracellular region that can be organized into three tandem repeats of immunoglobulin-like domains and eight tandem repeats of fibronectin type III-like domains. In the brain, the major transcript of PTP sigma is an alternatively spliced mRNA, in which the coding region for the fibronectin type III-like domains number four to seven are spliced out, thus coding for a protein of 1502 amino acid residues similar to the rat PTP sigma and rat PTP-NE3. Using in situ hybridization, we assigned hPTP sigma to chromosome 6, arm 6q and band 6q15. The bacterial-expressed hPTP sigma exhibits PTPase activity that was inhibited by orthovanadate (IC50 = 0.02 microM) and by two bisphosphonates used for the treatment of bone diseases, alendronate (ALN) (IC50 = 0.5 microM) and etidronate (IC50 = 0.2 microM). In quiescent calvaria osteoblasts, micromolar concentrations of vanadate, ALN and etidronate stimulate cellular proliferation. These findings show tissue-specific alternative splicing of PTP sigma and suggest that PTPs are putative targets of bisphosphonate action.
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PMID:Human protein tyrosine phosphatase-sigma: alternative splicing and inhibition by bisphosphonates. 899 85

Multiple genetic alterations, including concurrent inactivation of RB and p53, occur frequently in several human cancers. To investigate the biological significance of RB and p53 gene inactivations, a wild-type RB or p53 cDNA expression vector regulated by tetracycline was introduced by stable transfection into an osteosarcoma cell line Saos-2, in which both the RB and p53 genes were inactivated. Induction of introduced RB expression resulted in suppression of cell growth, increased percentage of cells at the G0/G1 phase, and enlargement of the cells. Furthermore, activity of alkaline phosphatase was increased and expression of fibronectin was decreased, suggesting the induction of cell differentiation by RB expression. Induction of p53 expression also resulted in significant suppression of cell growth with slight accumulation of cells at the G0/G1 and G2/M phases. The cells were detached from culture dishes and the dead cell fraction increased. Furthermore, condensation of chromatin and DNA fragmentation were observed, suggesting the induction of apoptosis by p53. These results suggest that RB and p53 play different roles in carcinogenesis of osteoblast; RB inactivation releases cells from G0/G1 arrest and suppresses cell differentiation while p53 inactivation assists the cells to proliferate by repressing both apoptosis and cell cycle arrest at G0/G1 and G2/M.
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PMID:Differentiation induced by RB expression and apoptosis induced by p53 expression in an osteosarcoma cell line. 913 82


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