Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The abilities of malignant tumor cells to bind and migrate through basement membranes are important steps in invasion and metastasis. Malignant tumor cells would therefore be expected to express receptors on their surfaces for basement membrane and stromal components, such as collagens, laminin, and fibronectin, although the pattern of expression of these receptors on the malignant cells may be different from that on their normal progenitors. We report here that chemically transformed tumorigenic human cells express an altered pattern of integrin receptors on their cell surfaces as compared with their untransformed nontumorigenic counterparts. Specifically, N-methyl-N'-nitro-N-nitrosoguanidine transformation of HOS cells into highly tumorigenic cells results in a significant specific increase in the expression of (in descending order of level of cell surface expression) the integrins alpha 6/beta 1, alpha 2/beta 1, and alpha 1/beta 1, which are receptors for laminin, collagens, and collagen type IV and laminin, respectively. The level of expression of two fibronectin receptor integrins, alpha 5/beta 1 and alpha 3/beta 1, are, however, unaltered, whereas the level of expression of vitronectin receptor integrin, alpha v/beta 3, is drastically reduced on the transformed cells. Consistent with the increased expression of laminin and collagen receptors and the decreased expression of vitronectin receptors on the transformed cells, these cells attached three- to fivefold more strongly to laminin and collagen but attached very poorly to vitronectin. The MNNG-HOS cells were also found to have a greater potential for invasion through reconstituted basement membrane, matrigel, the major components of which are laminin and type IV collagen. The invasion of both the HOS and MNNG-HOS cells was inhibited 45-50% by a polyclonal anti-fibronectin receptor antibody. However, although the invasion of HOS cells could be inhibited up to 75% by an anti-alpha 6 monoclonal antibody, a similar concentration of this antibody had no effect on the alpha 6-overproducing MNNG-HOS cells. A fivefold higher concentration of this antibody did result in partial inhibition of MNNG-HOS invasion. These data indicate a critical role for the alpha 6/beta 1 laminin receptor in the invasion of these cells through basement membranes and demonstrate that chemical transformation of nontumorigenic human cells to highly tumorigenic cells is associated with an altered pattern of integrin expression which may play a direct role in the increased capacity of these cells to bind and invade through basement membranes.
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PMID:Alterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes. 168 58

Expression of urokinase-type plasminogen activator (u-PA) strongly correlates with a malignant tumor cell phenotype. In the multistep process of metastasis, different cellular functions are influenced by urokinase. The enzyme is known to be effective via both proteolytical and signal transduction mechanisms. In the present study, the osteosarcoma cell line MNNG/HOS was transfected with a vector capable of expressing an antisense transcript, complementary to 1,021 bases of the 3' end of u-PA cDNA. This construct was most effective in reducing u-PA expression in previous experiments. Stably transfected antisense (as) cell lines were characterized and compared with the parental MNNG/HOS. Antisense transfection of MNNG/HOS gave the following results: (1) stable incorporation of the construct into the genome of as-clones, as detected by Southern blot analysis; (2) decreased mRNA level of u-PA, as detected by Northern blot analysis; (3) approximately 50% reduced enzyme expression in cell culture medium and cell homogenate; and (4) unchanged cellular proliferation activity and u-PAR expression. In further functional analysis, as-clones showed (1) significantly reduced invasion and motility in modified Transwell chambers (random migration and chemotaxis with collagen I as a chemoattractant); (2) significantly reduced adhesion on matrices of collagen I and vitronectin; (3) unchanged adhesion properties on Matrigel matrix; and (4) reduced metastatic potential to lungs and especially liver in chick embryos after i.v. infection into chorioallantoic membrane veins. Our data show that in MNNG/HOS urokinase influences cellular malignancy by promoting migration and selective adhesion. These specific functions were notable in addition to the effects on invasion and basement membrane degradation.
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PMID:Antisense inhibition of urokinase: effect on malignancy in a human osteosarcoma cell line. 963 7

In the multistep process of tumor metastasis, different cellular functions are known to be influenced by the urokinase plasminogen activator (u-PA). In different types of malignancies, u-PA has been shown to correlate strongly with a malignant tumor cell phenotype. Besides its proteolytic activity, the enzyme is effective by signal transduction mechanisms. To elucidate u-PA functions in osteosarcoma, in the present study, the osteosarcoma cell line MNNG/HOS was transfected with an antisense (as) expression vector encoding the 3' end of u-PA-cDNA. Several stably transfected cell clones were characterized and compared with the parental cell line. The antisense transfection resulted in: (1) stable incorporation of the vector construct into cellular genome, as demonstrated in Southern blot; (2) decreased u-PA expression in Northern blot; (3) 50% reduced u-PA protein expression in both cell homogenate and cell culture medium; (4) unchanged cellular proliferation and u-PAR (urokinase plasminogen activator receptor) expression. In comparing functional analysis, as-clones showed (I) significant reduced in vitro invasion and motility (chemotaxis with collagen I); (II) significantly reduced adhesion activity to both vitronectin and collagen I matrices but unchanged adhesion on matrigel; (III) reduced in vivo metastasis in chick embryos after i.v.-application. All together, this data show that malignancy of the osteosarcoma cell line MNNG/HOS is positively influenced by urokinase in terms of migration and selective adhesion. Both effects were observed besides the previously described enzyme functions in tumor cell invasion and basement membrane degradation.
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PMID:[Antisense inhibition of urokinase in a human osteosarcoma cell line]. 1009 29

Hydroxyapatite (HA) is an osteoconductive implant material. We previously demonstrated that RGD peptides regulate the spreading of HOS cells on HA but not on titanium, speculating that the osteoconductivity of HA might be attributed to this RGD domain-dependent spreading of osteoblasts. To confirm this hypothesis, the molecules which regulate the spreading of HOS cells on HA and on titanium were investigated. The 50% effective dose (ED50) of RGD peptide for the spreading on HA was five fold lower comparing to titanium. Anti-alphaV integrin antibody, vitronectin, and fibronectin inhibited the spreading on HA but not on titanium. In Western blot analysis, vitronectin and fibronectin were found in components adsorbed to HA but not to titanium. Taken together, the spreading of HOS cells on HA but not on titanium requires the interaction of alphaV integrin and its ligands. The ED50 of the RGD peptides on titanium but not on HA was remarkably reduced by neuraminidase treatment, that by itself could not inhibit the spreading on both materials. This phenomenon suggests that RGD domain and sialic acid cooperatively but not independently mediate the spreading of HOS cells on titanium. Collectively, the molecules regulating the spreading on HA are apparently different from those on titanium. The spreading of osteoblasts mediated by RGD domain of vitronectin and fibronectin might contribute to the osteoconductive ability of HA.
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PMID:Diverse mechanisms of osteoblast spreading on hydroxyapatite and titanium. 1081 64

We used an adhesion assay for cells cultured under high dynamic strain to measure human osteoblast-like HOS cell adherence to immobilized type I collagen, fibronectin, and vitronectin. These conditions were designed to model the increased forces present at unstable fractures or loose joint prostheses. At a constant, low protein-coating density (1000 molecules/microm2) and 20% cyclic strain for 24 h, type I collagen, fibronectin, and vitronectin supported 24.6 +/- 2%, 16.7 +/- 3%, and 1.1 +/- 1% adherence, respectively, which paralleled the relative number of integrin-binding sites in each protein. Thus, when the number of available binding sites was limited, strain resistance was proportional to the number of integrin-ligand interactions. In contrast, at high protein-coating densities (> or = 2,500 molecules/microm2), vitronectin supported greater adherence (45.7 +/- 2%) when compared with type I collagen (37 +/- 2%) or fibronectin (34.8 +/- 2%) and directed constitutive expression of osteopontin (OPN), which suggested that there exist discrete signals on vitronectin receptor occupancy that promoted cell adherence and survival under strain. Integrin-mediated binding was necessary for resistance to strain, as evidenced by the low levels of strain resistance observed when cells were adherent in a nonintegrin-dependent manner. These findings support the utilization of at least two distinct mechanisms (i.e., tensegrity and integrin-mediated signal transduction) by HOS cells to remain adherent and viable on exposure to mechanical forces.
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PMID:A comparison of type I collagen, fibronectin, and vitronectin in supporting adhesion of mechanically strained osteoblasts. 1187 39

In this study, we evaluated early bone responses to a vitronectin-derived, minimal core bioactive peptide, RVYFFKGKQYWE motif (VnP-16), both in vitro and in vivo, when the peptide was treated on sandblasted, large-grit, acid-etched (SLA) titanium surfaces. Four surface types of titanium discs and of titanium screw-shaped implants were prepared: control, SLA, scrambled peptide-treated, and VnP-16-treated surfaces. Cellular responses, such as attachment, spreading, migration, and viability of human osteoblast-like HOS and MG63 cells were evaluated in vitro on the titanium discs. Using the rabbit tibia model with the split plot design, the implants were inserted into the tibiae of four New Zealand white rabbits. After two weeks of implant insertion, the rabbits were sacrificed, the undecalcified specimens were prepared for light microscopy, and the histomorphometric data were measured. Analysis of variance tests were used for the quantitative evaluations in this study. VnP-16 was non-cytotoxic and promoted attachment and spreading of the human osteoblast-like cells. The VnP-16-treated SLA implants showed no antigenic activities at the interfaces between the bones and the implants and indicated excellent bone-to-implant contact ratios, the means of which were significantly higher than those in the SP-treated implants. VnP-16 reinforces the osteogenic potential of the SLA titanium dental implant.
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PMID:A Vitronectin-Derived Bioactive Peptide Improves Bone Healing Capacity of SLA Titanium Surfaces. 3162 47