Requirement of Receptor-bound Urokinase-type Plasminogen Activator for Integrin αvβ5-directed Cell Migration

Yebra, Mayra; Parry, Graham; Strömblad, Staffan; Mackman, Nigel; Rosenberg, Steven; Mueller, Barbara M.; Cheresh, David A.

doi:10.1074/jbc.271.46.29393

Cited by 239 publications

(155 citation statements)

References 49 publications

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“…In addition, it has been found that uPA/uPAR complexes bind vitronectin (which in turn binds to the same av integrins as osteopontin), and that uPAR may itself physically associate with certain integrins, such that some have suggested that uPA may stimulate cell migration and invasion by non-proteolytic mechanisms as well (e.g. by modulating adhesion interactions at focal contacts, or by triggering signal transduction pathways involved in the motility response) (Andreasen et al, 1997;Yebra et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells

et al. 1999

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Osteopontin (OPN) has been associated with enhanced malignancy in breast cancer, but its functional role in this disease is poorly understood. To study the e ect of OPN on cellular invasiveness, basal OPN expression was ®rst assessed in members of a progression series of human mammary epithelial cell lines (21PT: immortalized, non-tumorigenic; 21NT: weakly tumorigenic; 21MT-1: tumorigenic, weakly metastatic; MDA-MB-435 cells: tumorigenic, highly metastatic). The two lines which expressed lowest basal levels of OPN (21PT, 21NT) were then examined for up-regulation of invasive behavior in response to exogenous or transfected (endogenous) OPN. Both 21PT and 21NT showed increased invasiveness through Matrigel when human recombinant (hr)OPN was added to the lower chamber of transwells. Both also showed a cell migration response to hrOPN. Populations of 21PT and 21NT cells stably transfected with an OPN-expression vector showed higher levels of cell invasiness than control vector transfectants. Examination of transfectants for mRNA of a number of secreted proteases showed that only urokinase-type plasminogen activator (uPA) expression was closely associated with OPN expression and cellular invasiveness. Treatment of the parental 21PT and 21NT cells with exogenous hrOPN resulted in increased uPA mRNA expression and increased urokinase activity of the conditioned media. Both increased cell migration and induction of uPA expression are thus potential mechanisms of increased invasiness of breast epithelial cells in response to OPN.

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Section: Discussionmentioning

confidence: 99%

Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells

et al. 1999

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“…25,60,61 The uPA receptor then focuses plasmin activation at or near the sites of focal contact between cell surface and extracellular matrix proteins. 62,63 Recent results have shown that vitronectin plays a crucial role in directing the redistribution of integrins and uPA to focal adhesion sites in several cancer cell lines, including PC cell lines. 63 Once co-localized to focal points, uPA is thought to regulate cell migration as well as pericellular proteolysis by co-ordinating focal detachment.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Sabbisetti

Chigurupati

Thomas

et al. 2006

Intl Journal of Cancer

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Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several folds higher than that in benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation increases invasiveness of prostate cancer (PC) cells via activation of protein kinase A. Since the role of urokinase-type plasminogen activator (uPA) in invasion of PC has been established, we tested the hypothesis that CT increases invasion of PC cells by stimulating uPA secretion from PC cells. Exogenously added CT stimulated the secretion of uPA from PC-3M cells in a dose-dependent manner, which was blocked by Rp.cAMP, a competitive inhibitor of protein kinase A. CT stimulated the secretion of MMP-2 and MMP-9 from PC-3M cells, and also increased their invasiveness. Both these actions of CT were blocked by uPA-neutralizing antibodies. Immunofluorescence studies with PC-3M cells suggest that CT stimulated redistribution of cellular uPA to focal adhesion sites, which was further confirmed by co-immunoprecipitation of uPA with focal adhesion kinase (FAK) in response to CT. These results suggest that CT increases invasiveness of PC cells by stimulating PKA-mediated uPA secretion and by redirecting the secreted uPA to focal adhesion sites. The results also suggest that uPA may, at least in part, mediate proinvasive actions of CT on PC cells by stimulating the secretion of gelatinases and degradation of focal adhesion sites. ' 2005 Wiley-Liss, Inc.

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“…45,46 In addition, uPA or plasmin is known to stimulate cell motility. 42,47,48 In vitro invasion of Matrigel, a reconstituted basement membrane, by HOXϩ1 and HOXϩ2 cells was enhanced by addition of plasminogen into the medium during the assay. Taken together, uPA and integrin ␤3 induced by HOXD3 overexpression are considered important factors involved in the marked enhancement of invasive and metastatic capacity.…”

Section: Matrix-degradative Property Of the Hoxd3 Transfectantmentioning

confidence: 99%

Overexpression of homeobox geneHOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells

et al. 2001

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Homeobox-containing genes are expressed in spatiotemporal fashion during embryogenesis and act as master transcription-regulating factors which control the expression of a variety of genes involved in morphogenesis. They are also expressed in a tissue-specific manner in normal adult tissues and appear to give cells spatial information in the maintenance of their architectural integrity. We transfected a HOXD3 class I homeobox-containing gene into human lung cancer A549 cells and investigated alterations in gene expressions and phenotypes related to the maintenance of tissue architecture in HOXD3-overexpressing A549 cells. In the HOXD3-overexpressing cell lines, expression of E-cadherin was lost and plakoglobin was strongly repressed, whereas integrin ␣3 and ␤3 were up-regulated and N-cadherin and integrin ␣4 were newly expressed. Compared with parental and control transfectant lines, the HOXD3-overexpressing cell lines showed highly motile and invasive activity. Blocking experiments using anti-integrin ␤1 and ␤3 suggested that the increased haptotaxis of the HOXD3-overexpressing cells to vitronectin resulted from increased expression and activation of integrin ␣v␤3, and that overexpression of the HOXD3 gene converted the integrin ␤1-dependent haptotaxis to fibronectin into both integrin ␤1-and ␤3-dependent one. HOXD3 overexpression increased production of matrix-degrative enzymes including matrix metalloproteinase-2 and urokinase-plasminogen activator. When the tumor cells were intravenously injected into the tail veins of nude mice, HOXD3 transfectants formed a significantly large number of metastatic foci in lungs compared with the control transfectants. These findings suggest that HOXD3 can act as a metastasis-promoting gene in human lung cancer A549 cells.

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Requirement of Receptor-bound Urokinase-type Plasminogen Activator for Integrin αvβ5-directed Cell Migration

Cited by 239 publications

References 49 publications

Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells

Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Overexpression of homeobox geneHOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells

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