• Archives of Pharmacal Research
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• v.18 no.6
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• pp.376-380
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• 1995

Monocyte adhesion involves specific cell surface receptors, integrins and results in cell differentiation. We have studied expression and regulation of integrin .${\alpha}_5{\beta}_1$ during differntiation of U937 as in vitro model. To determine expression of integrin ${\alpha}_5{\beta}_1$ during differentiation of U937 as in vitro model. To determine expression of integrin ${\alpha}_5{\beta}_1$ genes by RT-PCR (reverse transcription and polymerase chain reaction) method. We determined expression of integrin ${\alpha}_5{\beta}_1$ genes by RT-PCE (reverse transcription and polymerase chain reaction) method. We found that expression of integrin .alpha.5.betha.1 was greatly increased during PMA-induced differentiation of U937 cells and also found that PMA-induced expression of integrin ${\alpha}_5{\beta}_1$ was inhibited by colchicine, microtubule depoly merizing agent. These results indicate that microtubular integrity is associated with expression of integrin. ${\alpha}_5{\beta}_1$ during PMA-induced differentiation of U937 cells.

• Korean Journal of Head & Neck Oncology
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• v.13 no.2
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• pp.169-179
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• 1997

서론 : Laminin의 수용기로 알려진 Integrin $\alpha6\beta4$의 세포내 표현 정도는 편평상피암을 위시한 여러 악성종양의 전이능력 및 예후와 밀접한 상관관계가 없다고 알려져 있다. 이 Integrin은 Laminin과 같은 세포와 리간드와 결합하면 상피세포의 기저막 지주 구조물인 hemidesmosome의 세포체질 요소(cytoskeletal element)와 연관되어 그 결과 세포의 기저막과 세포내 케라틴을 연결하는 역할을 한다. Integrin $\alpha6\beta4$는 구조적으로 다른 많은 integrin들과 달리 $\beta$4의 세포질내 영역(cytoplasmic domain)이 특징적으로 크다. 이 세포질내 영역 $\beta$4 integrin의 기능은 아직 밝혀지지 않고 있으나 아마 세포 성장의 신호전달 및 악성종양의 특징인 침윤 전이에 관련할 것으로 보아지고 있다. 재료 및 방법: 저자들은 우선 $\beta$4 integrin의 wild type s-DNA와 $\beta$4 세포질내 영역(cytoplasmic domain) 및 $\beta$4의 tyrosine 인산화 반응 부위가 각각 결손된 c-DNA를 PCR을 통하여 합성하여 pRc/CMV 벡터에 삽입한 후 원래 $\beta$4 integrin의 발현이 결집된 인간 방광암 세포에 Calcium phosphate precipitation 방법으로 주입(transfection)시켜 형질변환된 세포를 면역형광법, Flow cytometry 및 Immunoprecipitation 방법으로 클로닝하여 wild type $\beta$4-full length(Clone FL), truncated $\beta$4-cytoplasmic domain(C1one CD), 및 mutated $\beta$4-tyrosine phosphorylation site (Clone M)을 얻었다. 암 세포의 부착 및 침투 능력의 기능적 연구로 모노 클로날 항체와 fibronectin, laminin, Matrigel을 단백질 기질로 사용하였으며 결과 비교를 위하여 pRc/CMV 벡터만 주입시켰던 클로운과 방광암 세포주를 $\beta$4 integrin 음성 대조군으로 또한 이 Integrin의 높은 발현을 보이는 두경부 편평상피암 세포주를 양성 대조군으로 이용하였다. 결과 : 세포부착능력에 있어서 온전한 $\beta$4 cytoplasmic domain이 존재하는 클로운이 laminin에 강한 부착능력을 보였으나 fibronectin의 부착정도는 $\beta$4 integrin의 표현정도와 관계없이 모든 클로운에서 비슷하였다. Matrigel을 투과하는 암세포 침윤 능력에서는 $\beta$4 integrin의 표현이 존재하는 클로운들이 투과 능력이 높았으나 세포외 리간드가 없는 control membrane을 사용하였을 때와 비교하여 투과능력의 차이를 보이지 않았다. 결론 : 유전자 주입(transfection) 방법으로 integrin의 다양한 클로운의 합성이 가능하여 이 Integrin의 암 세포의 부착 및 침투 능력에서의 기능을 규명 할 수 있게 한다. $\beta$4 integrin은 편평상피 암세포의 부착에 있어서 세포외 리간드 laminin과 특이 결합하여 부착 능력을 높이는 중요한 역할을 하며 편평상피 암세포의 침투에 있어서는 $\beta$4 integrin의 표현이 침투 능력을 높이는 역할을 하나 이때에는 laminin과 같은 리간드와의 특이 결합에 의존하지는 않는 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3891-3895
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• 2013

The purpose of this study was to evaluate the association of expression of ${\alpha}5{\beta}1$-integrin with clinicopathologic features and prognosis in cervical cancer. Levels of ${\alpha}5{\beta}1$-integrin in normal cervical mucosa and cervical cancer tissue were detected with immunohistochemistry. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. ${\alpha}5{\beta}1$-integrin expression was detected in 84.6% (143/169) cervical cancer samples, significantly different from that in normal cervical mucosa (P < 0.05). Positive expression rates of ${\alpha}5{\beta}1$-integrin in patients with poor histologic differentiation, lymph node metastasis, and recurrence were elevated. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expression of ${\alpha}5{\beta}1$-integrin revealed a highly significant difference in human cervical cancer cases (P < 0.05), suggesting that overexpression of ${\alpha}5{\beta}1$-integrin is associated with a worse prognosis.The ${\alpha}5{\beta}1$-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of cervical cancer. The current study indicated that ${\alpha}5{\beta}1$-integrin may be an independent prognostic factor for cervical cancer patients.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.55-66
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• 1998

Pathophysiological mechanism of hemorrhagic fever with renal syndrome (HFRS) is not fully understood. Major clinical findings of HFRS patients are widespread hemorrhage, acute renal failure and shock. Basic lesion is vascular injury with microvascular hemorrhage and relatively little inflammation. According to autopsy findings, renal medulla shows focal hemorrhage, tubular necrosis and interstitial mononuclear infiltrates. The predominant cell type in the renal and pulmonary interstitium is a fibroblast and it participates in the healing process at the injury site by secreting a large amount of extracellular matrix proteins. Cultured human lung fibroblasts and Mongolian gerbil fibroblasts were known to be good host cells for the hantaan virus. It is possible that not only the endothelial cell but also the fibroblast is a target of Hantaan virus and the fibroblast might be involved in the pathogenesis and the healing process in HFRS. Integrins are adhesion molecules, and act as receptors for many extracellular matrix proteins. Recently, there are many reports that cell surface integrins influence on some viral infections or reversely viruses influence on the expression of integrins. The ${\alpha}_5{\beta}_1$ integrin is a major receptor for the fibronectin which is an important extracellular matrix protein secreted by fibroblasts. In this study, the role of ${\alpha}_5{\beta}_1$ integrin in the infection of Hantaan virus was examined by using anti-${\alpha}_5{\beta}_1$, integrin, anti-${\alpha}_5$ integrin and anti-${\beta}_1$, integrin antibodies in chicken embryo fibroblasts (CEF) and Mongolian gerbil fibroblasts(MGF). The treatment of anti-${\alpha}_5{\beta}_1$, integrin antibody in CEF reduced the virion titers 26.8% and the amount of nucleocapsid N protein 32.6% when compared with control CEF. When MGF were treated with anti-${\alpha}_5$, anti-${\beta}_1$ and anti-${\alpha}_5{\beta}_1$ integrin antibodies, virion titers were reduced by 26.5%, 29.4% and 28.7% and the amount of nucleocapsid N protein were reduced by 65.2%, 59.7% and 72.6%. These results suggested that ${\alpha}_5{\beta}_1$ integrin might act as a receptor for the Hantaan virus or blocking of ${\alpha}_5{\beta}_1$ integrin influences on the viral replication in CEF and MGF. It is also possible that the blocking of only one subunit of integrin represents similar results in that of whole molecule.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.140-148
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• 2000

Objectives : This experiment was conducted to investigate the suppressive effects of Dangguijakyak-san and Wuelbigachul-tang on the expression of ICAM-l and ${\beta}1-integrin$, which mediate cell-cell or cell-matrix interaction, and on the proliferation of mesangial cells. Methods : After in vitro culturing of human mesangial cells with the supernatant which was obtained from the monocytes separated from human blood with Con-A, hydrocortisone, Dangguijakyak-san and Wuelbigachul-tang respectively, we evaluated suppressive effects by measuring the mesangial cell surface enzyme immunoassay or flow cytometry. Results : The results are summarized as follows: 1. Dangguijakyak-san and Wuelbigachul-tang induced marked suppressive effects on the mesangial cell proliferation in the 50% and 25% supernatant concentration stimulating experiments, but hydrocortisone had little effect in these experiments. 2. Dangguijakyak-san and Wuelbigachul-tang induced marked suppressive effects on ICAM-l and ${\beta}1-integrin$ expression, but were less effective than hydrocortisone was. Conclusions : Based on these results, Dangguijakyak-san and Wuelbigachul-tang were found to be effective in the suppression of mesangial cell proliferation and in ICAM-1 and ${\beta}1-integrin$ expression. Further in vitro investigations as conducted above, with the in vivo experiments reflected, may prove that Dangguijakyak-san and Wuelbigachul-tang contribute to the prevention of the glomerular disease.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.321-328
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• 2017

Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin ${\beta}1$ and fibronectin, a ligand of integrin ${\alpha}5{\beta}1$. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin ${\beta}1$ and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin ${\beta}1$ and activation of FAK.

• Journal of Korean Neurosurgical Society
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• v.57 no.5
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• pp.329-334
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• 2015

Objective : To comparatively investigate the expression of several integrins in specimens of human bone metastases and degenerative bone tissue. Methods : Degenerative cancellous tissue was obtained from a sample of human degenerative spine. Thirteen human specimens were obtained from metastatic spine tumors, whose primary cancer was colon cancer (n=3), hepatocellular cancer (n=3), lung cancer (n=4), and breast cancer (n=3). The expression of vimentin and integrins ${\alpha}v$, ${\beta}1$, and ${\beta}3$ was assessed in metastatic and degenerative specimens by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results : Immunohistochemical staining showed that vimentin and integrin ${\alpha}v$ was broadly expressed in all tissues examined. By contrast, integrin ${\beta}1$ was weakly expressed only in 38.4% (5/13) of tissues. Integrin ${\beta}3$ was consistently negative in all cases examined. qRT-PCR analysis showed that vimentin gene expression was higher in all metastatic specimens, as compared to degenerative bone. The gene expression of integrin ${\alpha}v$ in breast specimen was significantly higher than others (p=0.045). The gene expression of integrin ${\beta}1$ was also higher in all metastatic specimens than in degenerative bone tissue. The gene expression of integrin ${\beta}3$ was variable. Conclusion : Spinal metastatic tumors have mesenchymal characteristics such as increased expression of vimentin. The increased expression of integrin ${\alpha}v$ and ${\beta}1$ in spine metastatic tumors suggests that adhesive molecules such as integrin may have implications for the prevention of spine metastasis.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.40-50
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• 2000

Objectives : The progression of renal disease can be identified as a glomerulosclerosis by histological examination, and the basic mechanism of glomerulosclerosis is mesangial cell proliferation and mesangial matrix accumulation. ICAM-1, ${\beta}1-integrin$ and MHC-class II are known to attribute to the progression of glomerulosclerosis. They mediate cell-cell or cell-matrix interactions and are expressed in response to injury and inflammation. Up to now, there have been few satisfactory regimens to treat glomerular diseases except minimal change nephrotic syndrome, which can be improved by steroid therapy. Studies were performed in order to investigate whether Jinmu-tang has suppressive effects on some factors associated with the progression of glomerular disease, mesangial cell proliferation, fibronectin synthesis, ICAM-1, ${\beta}1-integrin$ and MHC-class II expression. Methods : Studies were performed with the method of surface enzyme immunoassays or flow cytometry after addition of peripheral blood mononuclear cells(PBMC) supernatants treated with Jinmu-tang, using the cultured human mesangial cells. Results : 1. The suppressive effect of Jinmu-tang on mesangial cell proliferation was higher than that of hydrocortisone. 2. Jinmu-tang has some suppressive effects on fibronectin synthesis, ICAM-1, expression, ${\beta}1-integrin$ expression and MHC-class II expression of mesangial cells, but was lower than hydrocortisone. Conclusions : Jinmu-tang generally shows some immunosuppressive effects. We carefully suggest that the above prescription may be applied to prevent the progression of renal disease or can be used as an adjuvant of or a substitute for steroid therapy.

• BMB Reports
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• v.45 no.3
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• pp.159-164
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• 2012

CD99 is known to be involved in the regulation of cell-cell adhesion. However, it remains unclear whether CD99 controls cell-extracellular matrix adhesion. In this study, the effects of CD99 activation on cell-extracellular matrix adhesion were investigated. It was found that engagement of CD99 with the stimulating antibody YG32 downregulated the adhesion of MCF-7 cells to fibronectin, laminin and collagen IV in a dose-dependent manner. The CD99 effect on cell-ECM adhesion was inhibited by overexpression of the dominant negative form of CD99 or CD99 siRNA transfection. Treatment of cells with $Mn^{2+}$ or by ${\beta}_1$ integrin-stimulating antibody restored the inhibitory effect of CD99 on cell-ECM adhesion. Cross-linking CD99 inactivated ${\beta}_1$ integrin through conformational change. CD99 activation caused dephosphorylation at Tyr-397 in FAK, which was restored by the ${\beta}_1$ stimulating antibody. Taken together, these results provide the first evidence that CD99 inhibits cell-extracellular matrix adhesion by suppressing ${\beta}_1$ integrin affinity.

• The Korean Journal of Zoology
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• v.37 no.4
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• pp.592-596
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• 1994

The interaction between fibronectin (FN) and its receptors controls cell attachment and migration, two crucial events during monocyte development and differentiation. To investigate the functional role of FN and its receptor, we have studied adhesion of monocyte to two different regions of FN (38- and 85-kDa domain), as well as the expression of the integrin during monocle differentiation. Anti-integrin Rl subunit antibody completely blocked the attachment of FN-coated latex beads to macrophage, but the effect of anti-integrin u4 antibody was much less significant. Rat monocyte expressed integrin $u4\beta1$ predominantly, while macrophage expressed $\alpha5\beta1$ as analyzed tv flow cvtometer and western blot. From these results, it can be suggested that these two integrins plan different roles during monocyte differentiation.