PAI1 stimulates assembly of the fibronectin matrix in osteosarcoma cells through crosstalk between the αvβ5 and α5β1 integrins

Vial, Daniel; McKeown‐Longo, Paula J.

doi:10.1242/jcs.020149

Cited by 36 publications

(33 citation statements)

References 32 publications

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“…Therefore, by preventing the activation of both uPA and plasmin, Pai1 reduces tumor cell migration and invasion (43,45,46). Although other groups have reported prometastatic properties of Pai1 in other tumor types (47,48), our data support a metastasis suppressor role for Pai1 in STS.…”

Section: Methodssupporting

confidence: 54%

MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes

et al. 2014

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Section: Methodssupporting

confidence: 54%

MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes

et al. 2014

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“…1A. ⅱ) Few studies have investigated the relationship between PAI-1 and collagen IV, while most studies investigated the relationship between PAI-1 and fibronectin, vitronectin and laminin (1,8,11,35). ⅲ) Collagen IV is known to be rich in basal membrane (where cervical cancer occurs) (37), and collagen IV could be important for CSCs.…”

Section: Resultsmentioning

confidence: 99%

“…PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and it is involved in cancer invasion and metastasis, by remodeling the ECM through regulating plasmin (1,(6)(7)(8)(9)(10)(11)(12). The studies investigating CSCs are now increasing in various types of solid tumors including cervical cancer, and CSCs are thought to be involved in tumor recurrence and metastasis (17,18).…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulation of the PA system is related to disorders such as thrombosis, atherosclerosis and type 2 diabetes (2-5). In addition, it has been reported that PAI-1 is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin (6)(7)(8)(9)(10)(11)(12). Some studies reported that overexpression of PAI-1 correlated with poor prognosis in cancer patients, however, it is controversial (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

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Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells

Sato

Kawana

Adachi

et al. 2015

International Journal of Oncology

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Abstract. The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

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“…These experiments argue that the glomerular suPAR that is generated or deposited in the kidney in response to LPS is different from the recombinant one administered by Cathelin et al 2 An appealing possibility is that the vitronectin/suPAR complex is disrupted by acute phase rises in plasminogen activator inhibitor-1. Plasminogen activator inhibitor-1 competes with uPAR for vitronectin binding 13 ; thus, one might expect less vitronectin/ suPAR during an acute phase reaction. This scenario favors vitronectin/suPAR as the active principle in integrin activation.…”

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confidence: 99%