Non-RGD domains of osteopontin promote cell adhesion without involving αv integrins

Katagiri, Yohko U.; Murakami, Masaaki; Mori, Kiyoshi; Iizuka, Junko; Hara, Toyomichi; Tanaka, Kumiko; Jia, Wenyi; Chambers, Ann F.; Uede, Toshimitsu

doi:10.1002/(sici)1097-4644(199607)62:1<123::aid-jcb13>3.0.co;2-o

Cited by 50 publications

(26 citation statements)

References 21 publications

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“…It appears that OPN mainly interacts with CD44 and not with one of its other receptor targets, namely a v b 1 , a v b 3 or a v b 5 , to facilitate H-RasV12-mediated transformation of NIH3T3 cells. Evidence in support of our position come from the following observations: (1) CD44 blocking antibody impaired both foci formation and invasion; (2) knockdown of OPN expression by RNAi disrupted both foci formation and invasion; (3) foci formation and invasion were not impeded by blockade of the integrins with the GRGDS peptide; (4) H-RasV12 must upregulate OPN and an additional component(s) to initiate transformation since OPN was not sufficient on its own to stimulate foci formation, OPN plus H-RasV12 synergistically stimulated foci formation, and CD44 but not the a v -containing integrins was upregulated by H-RasV12; (5) RGDdeficient OPN which cannot interact with the integrins (Katagiri et al, 1996) was shown to bind to H-RasV12-transformed but not control NIH3T3 cells; and (6) RGD-deficient OPN-binding activity to H-RasV12-transformed cells was inhibited by the CD44 blocking antibody.…”

Section: Discussionmentioning

confidence: 99%

“…Wild-type OPN interacts with CD44 in an RGDindependent manner and with the integrins through its RGD domain, thus the RGD-deficient OPN will only bind to CD44 (Katagiri et al, 1996). In the absence of antibody pretreatment or presence of negative control ERK2 antibody, the vast majority of adherent HRasV12-transformed cells bound mutant OPN (compare DAPI staining in lower panel with corresponding upper panel depicting the same cells bound to fluorescent OPN, Figure 3a).…”

Section: Binding Of Rgd-deficient Opn To Cd44 In Nih3t3 Cellsmentioning

confidence: 99%

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Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Teramoto

Castellone

Malek³

et al. 2004

Oncogene

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Activated forms of Ras family members are prevalent in many cancers where Ras mutants transduce signals essential for transformation, angiogenesis, invasion and metastasis. As a cancer progression model, we used NIH3T3 cells to explore the mechanism of Ras-induced tumorigenesis. Ras family mutants H-RasV12 and Rit79L strongly induced foci formation, while Rho family mutants RhoA-QL, Rac1-QL and Cdc42-QL were less effective. A comparison of downstream transcriptional targets of Ras and Rho family members using a 26 383 element cDNA microarray revealed that the osteopontin (OPN) gene exhibited the best correlation between magnitude of gene expression change and level of foci formation (r ¼ 0.96, Po0.001). In association with H-RasV12-and Rit79L-mediated transformation, foci secreted OPN protein and upregulated the OPN receptor CD44, suggesting the novel initiation of an aberrant OPN-CD44-Rac autocrine pathway. In support of this were the following observations. First, RGD-deficient OPN protein-binding activity was present in H-RasV12-transformed cells but not in control cells, and binding activity was inhibited by the CD44 blocking antibody. Second, foci formation, cell invasion and Rac activity were induced by H-RasV12 and inhibited by the CD44 blocking antibody. Third, foci formation by H-RasV12 was substantially reduced by a short interfering RNA (siRNA) specifically targeting OPN expression for knockdown. Fourth, H-RasV12-mediated transformation was not blocked by the GRGDS peptide, suggesting that OPN effects were not mediated by the integrins. Lastly, OPN knockdown affected the downstream expression of 160 '2nd tier' genes, and at least a subset of these genes appears to be involved in transformation. Indeed, four genes were selected for knockdown, each resulting in a disruption of foci formation and/or invasion. These results underscore the role of aberrant autocrine signaling and transcriptional networking during tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Binding Of Rgd-deficient Opn To Cd44 In Nih3t3 Cellsmentioning

confidence: 99%

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Teramoto

Castellone

Malek³

et al. 2004

Oncogene

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“…15 Recombinant human PDGF-BB was purchased from R&D Systems. A monoclonal anti-rat OPN antibody (MPIIIB10) was from American Research Products.…”

Section: Reagentsmentioning

confidence: 91%

Enhanced Expression of Osteopontin in Human Diabetic Artery and Analysis of Its Functional Role in Accelerated Atherogenesis

Takemoto

Yokote

Nishimura

et al. 2000

ATVB

Self Cite

110

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Abstract-We have previously reported that high glucose stimulates osteopontin (OPN) expression through protein kinase C-dependent pathways as well as hexosamine pathways in cultured rat aortic smooth muscle cells. The finding prompted us to study in vivo expression of OPN in diabetes mellitus. In the present study, we found by immunohistochemistry that medial layers of the carotid arteries of streptozotocin-induced diabetic rats and the forearm arteries of diabetic patients stained positively for OPN antibodies, whereas the staining from arteries of control rats and nondiabetic patients was negative. We also found that OPN stimulated the migration and enhanced platelet-derived growth factor (PDGF)-mediated DNA synthesis of cultured rat aortic smooth muscle cells. OPN and PDGF synergistically activated focal adhesion kinase as well as extracellular signal-regulated kinase; this finding seems to explain the OPN-induced enhancement of PDGF-mediated DNA synthesis. Taken Key Words: diabetic macroangiopathy Ⅲ osteopontin Ⅲ platelet-derived growth factor Ⅲ vascular smooth muscle cells I t is generally accepted that diabetic patients often suffer from atherosclerotic vascular diseases, such as ischemic heart disease and arteriosclerosis obliterans. 1,2 It is also known that diabetic vascular lesions tend to undergo restenosis after angioplasty and that diffuse calcification of the affected arteries is a characteristic feature of diabetic vascular diseases. [3][4][5] However, the reason for the accelerated atherogenesis in diabetes mellitus has not been fully elucidated.Osteopontin (OPN) is a multifunctional phosphoprotein secreted by many cell types, such as osteoclasts, lymphocytes, macrophages, epithelial cells, and vascular smooth muscle cells (SMCs). 6 Overexpression of OPN has been found in several physiological as well as pathological conditions, including immunologic disorders, 7 neoplastic transformation, 8 progression of metastases, 8 formation of urinary stones, 9 and wound healing. 10 It has been reported that OPN protein and mRNA are expressed in the neointima as well as in calcified atheromatous plaque. 11 A neutralizing antibody against OPN has been found to inhibit rat carotid neointimal formation after endothelial denudation. 12 It has also been reported that OPN inhibits the calcification of vascular SMCs in culture. 13 These reports have suggested that OPN contributes not only to the tissue calcification process but also to the development of atherosclerosis, especially in the process of intimal thickening.We have recently reported that high glucose levels stimulate OPN expression through protein kinase C-dependent pathways as well as hexosamine pathways in cultured rat aortic SMCs. 14 The present study was undertaken to gain more insight into the mechanism of diabetic vascular complications. We first demonstrate that OPN protein is highly expressed in the medial layers of the arteries of diabetic rats and patients. Furthermore, OPN stimulates migration and enhances platelet-derived growth factor (PDG...

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“…51 At a multiplicity of infection of 10 000 VP/cell, gene transfer with the RGD-negative AE74 and AE73 viruses was slightly above the background, whatever the length of incubation time. In contrast, the control vector AE18 was able to achieve significant gene transfer at that high MOI, and increasing the incubation time from 1 to 48 h improved transduction by 5.6-fold.…”

Section: Infection Of Car-positive or -Negative Cells With Modified Vmentioning

confidence: 99%

Genetic manipulations of adenovirus type 5 fiber resulting in liver tropism attenuation

et al. 2003

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Non-RGD domains of osteopontin promote cell adhesion without involving αv integrins

Cited by 50 publications

References 21 publications

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Enhanced Expression of Osteopontin in Human Diabetic Artery and Analysis of Its Functional Role in Accelerated Atherogenesis

Genetic manipulations of adenovirus type 5 fiber resulting in liver tropism attenuation

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