Biomedical subjects

Y K Liu

Publications and source records attributed to Y K Liu.

At least 19 recordsLinked to original sources

PubMed2002

A comparative study of Y chromosome microdeletions in infertile males from two Chinese populations.

PURPOSE: To compare the prevalence and type of Y-microdeletions in Hong Kong and Shanghai men with severe male-factor infertility. METHODS: Seven Y-linked sequence tagged site (STS) primers and seven gene-specific primers were screened in 293 infertile males (139 from Hong Kong and 154 from Shanghai) and 161 fertile men (61 from Hong Kong and 100 from Shanghai). Serum FSH, LH, and testosterone levels were also measured in these men. RESULTS: The incidence of Yq microdeletions in nonobstructive azoospermic men from Hong Kong (8.5%) and Shanghai (6%) was similar. Yq microdeletions were observed in severe oligospermic patients (8.5%) from Hong Kong but not from Shanghai. Among the 9 Hong Kong men with Y-microdeletions, 8 had AZFc deletion and one had AZFb deletion. In contrast, 6 of 9 men from Shanghai with Y-microdeletions had AZFb deletion. The incidence of AZFb deletion among Y-microdeleted men was statistically different between the two populations. Two of the men with AZFb deletion also had AZFa and AZFc deletions. CONCLUSIONS: Regional variations in the type of Y-microdeletion existed between Hong Kong and Shanghai infertile males.

Adult↗

PubMed2001

Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma when high and low metastatic models are compared.

Recently, we found that chromosome 8p deletion might be associated with hepatocellular carcinoma (HCC) metastasis by analyzing the differences in chromosomal alterations between primary tumors and their matched metastatic lesions of HCC with comparative genomic hybridization (CGH) (Qin et al. 1999). To further confirm this interesting finding, the genomic changes of two models bearing human HCC with different metastatic potentials (LCI-D20 and LCI-D35), and the new human HCC cell line with high metastatic potential (MHCC97) were analyzed by CGH. Gains on 1q, 6q, 7p, and 8q, and losses on 13p, 14p, 19p, 21, and 22 were detected in both LCI-D20 and LCI-D35 models. However, high copy number amplification of a minimum region at 1q12-q22 and 12q, and deletions on 1p32-pter, 3p21-pter, 8p, 9p, 10q, 14q, and 15p were detected only in the LCI-D20 model. Gains on 1p21-p32, 2p13-p21, 6p12-pter, 9p, 15q, and 16q11-q21, and losses on 2p23-pter, 4q24-qter, 7q31-qter, 12q, 17p, and 18 were detected only in the LCI-D35 model. The chromosomal aberration patterns in the MHCC97 cell line were similar to its parent LCI-D20 model, except that gains on 19q and losses on 4, 5, 10q, and 13q were found only in the cell line. These results provide some indirect clues to the metastasis-related chromosomal aberrations of HCC and further support the finding that 8p deletion is associated with HCC metastasis. 1q12-22 and 12q might harbor a novel oncogene(s) that contributes to the development and progression of HCC. Amplification on 8q and deletions on 4q and 17p may be not necessary for HCC metastasis.

Animals↗

PubMed2001

Abnormal beta-catenin gene expression with invasiveness of primary hepatocellular carcinoma in China.

AIM: To study the abnormal expression of beta-catenin gene and its relationship ith invasiveness of primary hepatocellular carcinoma among Chinese people. METHODS: Thirty-four hepatocellular carcinoma (HCC) specimens and adjacent para-cancerous tissues, 4 normal liver tissues were immunohistochemically stained to study subcellular distribution of beta-catenin. Semiquantitive analysis of expression of beta-catenin gene exon 3 mRNA was examined by RT-PCR and in situ hybridization. The relationship between expressions of both beta-catenin protein, mRNA and clinicopathological characteristics of HCC was also analyzed. RESULTS: Immuno-histochemistry showed that all normal liver tissues and para-cancerous tissues examined displayed membranous type staining for beta-catenin protein, occasionally with weak expression in the cytoplasm. While 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei. The accumulated type Labling Index (LI) of cancer tissue and para-cancerous tissue was (59.9 +/- 26.3) and (18.3 +/- 9.7) respectively (P<0.01). Higher accumulated type LI was closely related with invasiveness of HCC. Results of RT-PCR showed the beta-catenin gene exon 3 mRNA Expression Index (EI) of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue. Using in situ hybridization, the signal corresponding to beta-catenin gene exon 3 mRNA was particularly strong in cytoplasm of HCC when compared with those of para-cancerous and normal liver tissues. Over expression of beta-catenin exon 3 was also found to be correlated with high metastatic potential of HCC. CONCLUSION: Abnormal expression of beta-catenin gene may contribute importantly to the invasiveness of HCC among Chinese people.

Cadherins↗

PubMed2001

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential.

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

Animals↗

PubMed2001

Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97.

AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.

Albumins↗

PubMed2000

Inhibitory effects of synthetic beta peptide on invasion and metastasis of liver cancer.

PURPOSE: To study the inhibitory effects of synthetic beta peptide on invasion and metastasis of liver cancer. METHODS: Membrane-type intercellular adhesion molecule-1 (ICAM-1) expression of SMMC-7721 cultured hepatoma cells (7721 cells) was detected by immunofluorescence cell flowmeter. The adhesion of 7721 cells to fibronectin (FN) was assayed by the MTT method. The adhesion of 7721 cells to 7721 cells, 7721 cells to endothelial cells, and 7721 cells to lymphocyte cells was detected by adhesion assay. LCI-D20 human liver cancer metastasis model in nude mice was used in this experiment. One hundred micrograms of beta peptide per mouse were injected subcutaneously after tumor was resected premetastatically or postmetastatically to observe its effect on liver cancer metastasis after hepatectomy. RESULTS: Membrane-type ICAM-1 expression of SMMC-7721 cells treated by beta peptide was lower than that of the untreated cells. The adhesion of 7721 cells to FN, 7721 cells to 7721 cells, 7721 cells to endothelial cells, and 7721 cells to lymphocyte cells was also lower in the beta peptide group than in the untreated group. CONCLUSIONS: beta Peptide can block the adhesion of 7721 cells to FN, 7721 cells to some host cells in vitro, and inhibit HCC metastasis of LCI-D20 model posthepatectomy in vivo, so it could potentially act as an antimetastasis drug.

Animals↗

PubMed2000

Expression of platelet-derived endothelial cell growth factor and vascular endothelial growth factor in hepatocellular carcinoma and portal vein tumor thrombus.

PURPOSE: Both platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) are known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We aimed at evaluating the gene expression of PD-ECGF and VEGF in hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS: Surgical specimens (28 HCC, 28 nontumorous liver tissues and 18 PVTT) were studied by Northern blot analysis. The levels of PD-ECGF mRNA and VEGF mRNA expression were measured by densitometric scanning of the autoradiographs, and they were normalized to the level of expression of an internal control (glyceraldehydephosphate dehydrogenase) mRNA. RESULTS: The expression rates of PD-ECGF mRNA in PVTT, HCC and nontumorous liver tissues were 77.8% (14/18), 67.9% (19/28) and 35.7% (10/28), being 88.9% (16/18), 75.0% (21/28) and 17.9% (5/28) respectively for VEGF mRNA. The expressions of PD-ECGF mRNA and VEGF mRNA were higher in HCC with PVTT than when PVTT was absent (P < 0.05). The PVTT was more often seen in patients with positive expression of both PD-ECGF mRNA and VEGF mRNA in HCC than in patients who were positive for only one of these factors or negative for both (P < 0.05). CONCLUSION: Both PD-ECGF and VEGF correlated well with the formation of PVTT of HCC.

Adult↗

PubMed2000

Preliminary communication. MRNA expression of MT1-MMP, MMP-9, cathepsin K, and TRAP in highly enriched osteoclasts cultured on several matrix proteins and ivory surfaces.

We demonstrated that the transcriptional expression of MT1-MMP, MMP-9, cathepsin K, and TRAP in highly enriched osteoclasts were regulated by different matrix proteins that bind to integrin on osteoclast, such as collagen type I (CoI), fibronectin (FN), vitronectin (VN), osteopontin (OPN), and ivory. Results suggested that the OPN-integrin alphavbeta3 binding plays a more important role than CoI-alpha2beta1 binding in the regulation of osteoclast activity.

Animals↗

PubMed2000

The targeted expression of interleukin-2 in human hepatocellular carcinoma cells.

To improve the safety and efficiency of human hepatocellular carcinoma (HCC) gene therapy, we explored the use of a liver-specific promoter and a tumor-specific enhancer to achieve regular IL-2 gene expression for treatment of HCC. The human alpha-fetoprotein (AFP) enhancer [E(AFP)] and the albumin promoter [P(ALB)] were amplified from human genomic DNA. We used eukaryotic expression vector pcDNA-3 for the delivery of the IL-2 gene because this plasmid is a non-transient, fast-selection expression vector. A recombinant plasmid was constructed including the selectable marker neoR gene and the human IL-2 gene derived by the E(AFP) - P(ALB). The liver-predominant expression pattern of the IL-2 gene was observed in the medium of the transfected cells. When human HCC cell lines displaying different levels of AFP and non-hepatocyte tumor cell lines were transfected with the recombinant plasmid, IL-2 was expressed highly in AFP and albumin-positive HCC cells, but low in nonhepatocyte tumor cells. Moreover, the expression level of IL-2 gene was positively proportional to the level of AFP expression in the transfected cells.

Albumins↗

PubMed1999

Invasion and metastasis of liver cancer: expression of intercellular adhesion molecule 1.

PURPOSE: To study the relationship between intercellular adhesion molecule 1 (ICAM-1) and liver cancer metastasis and to find predicting factors that could indicate the growth and metastasis of liver cancer. METHODS: ICAM-1 expression in fresh tissue of normal liver and hepatocellular cancer (HCC) was examined by immunoperoxidase staining. Serum soluble intercellular adhesion molecule 1 (sICAM-1) from patients with a benign HCC tumor, and the expression of ICAM-1 in the orthotopically transplanted LCI-D20 tumor of a nude mouse liver cancer metastasis model, and in human hepatoma, the tumor surrounding tissue and normal liver, was analyzed semiquantitatively by the immuno-dot blot method. Tissue ICAM-1 expression (mRNA level) was detected by Northern blotting. RESULTS: ICAM-1 expression in LD1-20 D metastatic liver cancer had a positive correlation with tumor size and the time after implantation. It increased suddenly as metastasis occurred being 3.03+/-0.51 before metastasis and 8.24+/-0.95 after metastasis, P < 0.01, then remained high, appending on the number of sites involved (monosite metastasis 5.48+/-0.49, multisite metastasis 10.05+/-1.17, P < 0.05). All six cases of normal liver samples were negative in anti-ICAM-1 immunohistochemical staining, 80.0% (36/45) of the HCC showed some ICAM-1 expression. The rate of positive cells was a little higher in large tumors, tumors with an intact capsule and tumors with metastasis, but there was no significant difference. It was noticed that two cancer emboli also had high ICAM-1 expression. The ICAM-1 concentration in HCC (13.43+/-0.09) was higher than that in tumor surrounding the liver (5.89+/-0.17, P < 0.01) and that in normal liver (4.27+/-0.21, P < 0.01). sICAM-1, like tissue ICAM-1, was higher in HCC patients than in patients (with benign liver tumor and normal controls. Both tissue ICAM-1 and sICAM-1 were higher in the metastasis group than in the group without metastasis (tissue ICAM-1 20.24+/-0.30 vs 10.23+/-0.12 P < 0.05; sICAM-1 12.18+/-0.25 vs 9.77+/-0.54 P < 0.05). Northern blot analysis revealed that ICAM-1 expression, as indicated by mRNA level, was also higher in HCC and in cancer emboli than in tumor surrounding liver and normal liver. CONCLUSIONS: Tissue ICAM-1 and serum sICAM-1 could indicate the stage of HCC, and the potential of hepatoma cells for invasion and metastasis. They may play an important role in the metastasis cascade.

Animals↗

PubMed1999

The targeted expression of the human interleukin-2/interferon alpha2b fused gene in alpha-fetoprotein-expressing hepatocellular carcinoma cells.

This study explores the use of a liver-specific albumin promoter and a tumor-specific alpha-fetoprotein (AFP) enhancer to achieve the regulated expression of the cytokine interleukin-2/interferon alpha2b (IL-2/IFNalpha2b) fused gene for treatment of hepatocellular carcinoma (HCC). The human AFP enhancer (E(AFP)) and albumin promoter (P(ALB)) were amplified from human chromosome DNA by the polymerase chain reaction. A recombinant retrovirus was constructed including, as a selectable marker, the neoR gene and the IL-2/IFNalpha2b fused gene controlled by E(AFP)-P(ALB). The liver-targeted expression pattern of the IL-2/IFNalpha2b fused gene was observed when this product was tested in the culture medium of the infected cells (IL-2 activity was 850 IU/10(6) cells, IFNalpha activity was 320 IU/10(6) cells). Moreover, The growth of the IL-2/IFNalpha2b-fused-gene-infected HCC cells, SMMC7721, was clearly suppressed by the second week after innoculation of nude mice compared to the control SMMC7721 cells infected with LXSN and untreated SMMC7721 cells (0.5 +/- 0.1 cm versus 1.4 +/- 0.2 cm and 1.6 +/- 0.2 cm, P < 0.05). The results showed that the combined transcriptional regulatory sequences of E(AFP)-P(ALB) could control the targeted expression of cytokine genes in AFP-positive human HCC cells, and the expression level of the IL-2/IFNalpha2b fused gene was positively correlated to the level of AFP expression in the infected cells. The IL-2/IFNalpha2b fused protein that was expressed has the functions of both IL-2 and IFNalpha. Therefore, this study illustrates the superiority of using transcriptionally targeted recombinant retrovirus vectors in cytokine-based gene therapy.

Albumins↗

PubMed1999

MAGE-1 and related MAGE gene expression may be associated with hepatocellular carcinoma.

PURPOSE: The possibility of tumor rejection antigen, encoded by the MAGE-1 gene, being a target for immunotherapy in hepatocellular carcinoma (HCC) patients and the cloning of the full-length cDNA of this gene for subsequent studies were explored with the aim of discovering new immunotherapeutic strategies for HCC. METHODS: Expression of the MAGE-1 gene in HCC specimens and HCC cell lines was examined by the reverse transcription/polymerase chain reaction (RT-PCR) with a pair of specific primers, which gave a 421-bp fragment. Another pair of primers were then used to amplify the full-length MAGE-1 cDNA by the same method. The PCR products were then digested by restriction endonucleases and inserted into the plasmid PUC19. After primary selection of the recombinants by endonuclease digestion, the sequences of the inserted gene fragments were confirmed by DNA sequence analysis. RESULTS: In 45 HCC patients, MAGE-1 mRNA was expressed in 27 tumor tissues (60%) and 5 paratumor tissues (11.1%). All the four HCC cell lines positively expressed the MAGE-1 gene. Owing to the high homology of the MAGE gene family, we obtained three clones of different MAGE genes using the same pair of cloning primers. The three clones were confirmed to be a full-length MAGE-1 gene, a 750-bp fragment of the MAGE-3 gene and a fragment highly homologous to MAGE-6 and MAGE-12 but not identical to any known MAGE genes. CONCLUSION: The high expression frequency of MAGE-1 gene in HCC suggests the possibility of using it as a target for immunotherapy in HCC patients. Some MAGE genes other than MAGE-1 may also be expressed in HCC together with an unknown MAGE gene that might introduce new targets for immune attacks. The three gene clones obtained in this study can be used in further investigations and especially in the development of new liver cancer vaccines.

Amino Acid Sequence↗

PubMed1999

New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis.

A new human hepatocellular carcinoma (HCC) cell line with a highly metastatic potential was established from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and growth in nude mice. The line, designated MHCC97, has been cultivated for 18 months and subcultured for more than 90 passages. The line was showed to be of human origin by karyotype analysis. The cells were either grown as compact colonies (in clusters) or as a monolayered sheet with about 31 h of population-doubling time, exhibited typical malignant epithelial in morphology and were positive for alpha-fetoprotein (AFP). Flow cytometric analysis of the cell DNA content showed an aneuploid pattern, and its index was 1.5 as compared to that of normal human peripheral blood lymphocytes. Karyotypic analyses of G- and C-banding techniques revealed that all cells presented chromosome abnormalities in number and structure. The number of cell line MHCC97 chromosome ranged from 59 to 65 with a modal number of 60 and 61. At least two common chromosome markers, i(1q) and der(4)t(4;?)(4pter-->q35::?), were present in all cells, and deletion of Y chromosome also occurred in all cells. The subcutaneous and intrahepatic xenografts were formed and metastatic lesions in lungs were found after the cells were inoculated into nude mice. The rate of metastasis to lungs was 100% using orthotopic inoculation. Reverse transcription polymerase chain reaction products revealed positive expressions of integrin alpha5 and beta1, urokinase type plasminogen activator receptor (uPAR), vascular endothelial growth factor and nm23-H1 mRNAs of cell line MHCC97. Immunostaining of c-Met, uPAR showed strongly positive in both subcutaneous xenografts and lung metastatic lesions; while positive in xenografts and negative in metastatic lesions for integrin alpha5, beta1. E-cadherin and P53 was not expressed either in xenograft or in the metastatic lesions. PCR products of HBsAg and HBxAg were both positive. The cell line MHCC97 still retained some characteristic features of original tumour. Establishment of cell line MHCC97 should be beneficial to the studies of HCC metastatic mechanisms.

Adult↗

PubMed1998

The expression of the mdm2 gene may be related to the aberration of the p53 gene in human hepatocellular carcinoma.

The relationship between mdm2 gene expression and p53 gene mutation in hepatocellular carcinoma (HCC) and their correlation with the invasiveness of the disease were investigated in this study. Either the expression level of the mdm2 gene or the mutation rate of the p53 gene was higher in HCC than in paratumor liver tissues. Studies on the relationship between mdm2 and p53 revealed that mdm2 gene expression in HCC without p53 mutation was higher than when there was p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was significantly lower than in HCC without mdm2 overexpression. Among 23 HCC with invasion, mdm2 gene overexpression was found in 6 patients while p53 mutation was found in the other 11 patients, and only 1 patient was found to have both mdm2 overexpression and p53 mutation. These results indicated that either mdm2 overexpression or p53 mutation may be related to the invasiveness of HCC. Considering that an autoregulatory feedback loop between the mdm2 and p53 genes may exist, wild-type P53 can induce the expression of mdm2 via a p53-binding site in the mdm2 gene, while MDM2 protein functions as a negative regulator of P53 protein. These results also suggest that mdm2 may be related to the high invasiveness of HCC through inactivating the tumor-suppressor function of the p53 gene.

Adult↗

PubMed1998

Static and dynamic bending responses of the human cervical spine.

The quasi-static and dynamic bending responses of the human mid-lower cervical spine were determined using cadaver intervertebral joints fixed at the base to a six-axis load cell. Flexion bending moment was applied to the superior end of the specimen using an electrohydraulic piston. Each specimen was tested under three cycles of quasi-static load-unload and one high-speed dynamic load. A total of five specimens were included in this study. The maximum intervertebral rotation ranged from 11.0 to 15.4 deg for quasi-static tests and from 22.9 to 34.4 deg for dynamic tests. The resulting peak moments at the center of the intervertebral joint ranged from 3.8 to 6.9 Nm for quasi-static tests and from 14.0 to 31.8 Nm for dynamic tests. The quasi-static stiffness ranged from 0.80 to 1.35 Nm/deg with a mean of 1.03 Nm/deg (+/- 0.11 Nm/deg). The dynamic stiffness ranged from 1.08 to 2.00 Nm/deg with a mean of 1.50 Nm/deg (+/- 0.17 Nm/deg). The differences between the two stiffnesses were statistically significant (p < 0.01). Exponential functions were derived to describe the quasi-static and dynamic moment-rotation responses. These results provide input data for lumped-parameter models and validation data for finite element models to better investigate the biomechanics of the human cervical spine.

Aged↗

PubMed1998

The abundance of NM23-H1 mRNA is related with in situ microenvironment and intrahepatic metastasis in hepato-cellular carcinoma.

In HCC specimens from 25 patients, the levels of nm23-H1 and H-ras mRNA were analyzed by quantitative reverse transcription-polymerase-chain reaction (RT-PCR). Tumor microvessel density (MDV), the essential factor of microenvironment and proliferating cell nucleus antigen (PCNA), indexes as tumor cell proliferating in its microenvironment are also analyzed by immunohistochemical methods using antibodies against endothelial protein factor VIII related antigen (F8RA) and antibody PC-10. Results show that The MDV and PCNA index in the group with intrahepatic metastasis is remarkably higher than that in without one (p<0.01), but the abundance of nm23-H mRNA is opposite (p<0.01). The abundance of H-ras mRNA shows little difference (p>0.05). MDV index shows directly relationship with PCNA index (p<0.01), the abundance of nm23-H1 mRNA show an inverse one with PCNA index (p<0.05). We conclude that in HCC, tumor in situ microenvironment, especially a deteriorative one, plays an important selective role. The decline of nm23-H1 mRNA abundance implies the increase of highly potential metastatic cancer cells which adapt to their microenvironment.

Biomarkers, Tumor↗

PubMed1997

Osteopontin involvement in integrin-mediated cell signaling and regulation of expression of alkaline phosphatase during early differentiation of UMR cells.

To clarify the function of osteopontin in osteoblast differentiation, we have examined the signal transduction pathway in an osteoblastic cell line (UMR106-6) bound to osteopontin, fibronectin, vitronectin and collagen type I surfaces. This was done by investigating the production and autophosphorylation of focal adhesion kinase (FAK) and the expression of alkaline phosphatase (ALP) at the transcription level. Results suggest that osteopontin was not only responsible for the autophosphorylation of FAK but regulated the expression of ALP, which was strongly correlated with FAK activity. These results suggest that osteopontin might act as a trigger in the early differentiation of osteoblasts.

Alkaline Phosphatase↗

PubMed1997

The binding ability to matrix proteins and the inhibitory effects on cell adhesion of synthetic peptides derived from a conserved sequence of integrins.

The beta peptide (113-125), derived from a conserved sequence of the beta subunit of integrins, was synthesized to investigate its adhesive properties to matrix proteins and the effects on cell adhesion to immobilized fibronectin. In this study, we observed that the biotinylated beta peptide was able to bind efficiently to immobilized fibronectin, fibrinogen, collagen Type I and vitronectin with different degrees of affinity. It was also demonstrated that biotinylated fibronectin or fibrinogen could bind to the coated beta peptide. This kind of binding, which might be non-covalent linkage, was partially blocked by coincubation with the peptide GRGDS or EDTA, but not by SDGRG. Cell adhesion experiments were performed to study the effect of the beta peptide. The data showed that the beta peptide partially inhibited both fibroblast L929 and MC3T3-E1 osteoblastic cells from adhering to immobilized fibronectin in a dosage-dependent manner. In the presence of 100 microM concentration of the beta peptide, the inhibition rate of cell adhesion was 34% for fibroblast L929 cells and 54.1% for MC 3T3-E1 osteoblastic cells. This research suggests that the beta peptide might act independently as an adhesive region of the beta subunit of integrins and may occupy the cell-binding site within fibronectin.

Amino Acid Sequence↗