Increased plasminogen binding is associated with metastatic breast cancer cells: differential expression of plasminogen binding proteins

Ranson, Marie; Andronicos, Nicholas M.; O'Mullane, Matthew J.; Baker, Mark S.

doi:10.1038/bjc.1998.261

Cited by 61 publications

(101 citation statements)

References 37 publications

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“…Glu-plasminogen was purified using lysine Sepharose 4B as described (Andronicos et al, 1997) and FITC-conjugated as described (Ranson et al, 1998) or Cy5-conjugated according to the manufacturer's instructions. The lysine-binding capacity of the fluorochrome-conjugated glu-plasminogen was verified by lysine Sepharose affinity chromatography and SDS-PAGE (data not shown).…”

Section: Purification and Labelling Of Proteinsmentioning

confidence: 99%

“…The MCF-7 and MDA-MB-231 human breast cancer cell lines were routinely cultured as previously described (Ranson et al, 1998). For all experiments cells were cultured for approximately 48 h in either flasks or on coverslips without a change of media.…”

Section: Cell Culturementioning

confidence: 99%

“…Both glu-plasminogen binding and immunocytometry assays were performed using dual colour flow cytometry with propidium iodide (PI) to distinguish between viable and non-viable cells as previously described (Ranson et al, 1998). The stability of gluplasminogen or plasmin activity on the surfaces of viable MDA-MB-231 cells at 37˚C was determined using a modification of the dual colour flow cytometry method.…”

Section: Flow Cytometry and Fluorimetrymentioning

confidence: 99%

“…Studies of the plasminogen activation cascade using human breast cancer cell lines have revealed insights into this cascade. The metastatic human breast cancer cell line MDA-MB-231 has a high glu-plasminogen binding capacity and cell surface uPA antigen levels (Ranson et al, 1998). This results in the generation of significant amounts of cell-surfaceassociated plasmin (Ranson et al, 1998) which facilitates the degradation of human endothelial basement membranes (Stonelake et al, 1997).…”

mentioning

confidence: 99%

“…Multiple proteins with glu-plasminogen binding activity have previously been detected by ligand blots in individual breast cancer cell lines (Ranson et al, 1998). A heterogeneous group of cellular plasminogen receptors has been identified and includes; actin, annexin II, cytokeratin 8, α-enolase, and tetranectin (reviewed in Felez, 1998).…”

mentioning

confidence: 99%

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The topology of plasminogen binding and activation on the surface of human breast cancer cells

Andronicos

Ranson

2001

Br J Cancer

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SummaryThe urokinase-dependent activation of plasminogen by breast cancer cells plays an important role in metastasis. We have previously shown that the metastatic breast cancer cell line MDA-MB-231 over-expresses urokinase and binds and efficiently activates plasminogen at the cell surface compared to non-metastatic cells. The aim of this study was to further characterise plasminogen binding and determine the topology of cell surface-bound plasminogen in terms of its potential for activation. The lysine-dependent binding of plasminogen at 4˚C to MDA-MB-231 cells was stable and resulted in an activation-susceptible conformation of plasminogen. Topologically, a fraction of bound plasminogen was co-localised with urokinase on the surfaces of MDA-MB-231 cells where it could be activated to plasmin. At 37˚C plasmin was rapidly lost from the cell surface. Apart from actin, other candidate plasminogen receptors were either not expressed or did not co-localise with plasminogen at the cell surface. Thus, based on co-localisation with urokinase, plasminogen binding is partitioned into two functional pools on the surface of MDA-MB-231 cells. In conclusion, these results shed further light on the functional organisation of the plasminogen activation cascade on the surface of a metastatic cancer cell.

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Section: Purification and Labelling Of Proteinsmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Flow Cytometry and Fluorimetrymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The topology of plasminogen binding and activation on the surface of human breast cancer cells

Andronicos

Ranson

2001

Br J Cancer

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Urokinase-type plasminogen activator and its receptor in colorectal cancer: Independent prognostic factors of metastasis and cancer-specific survival and potential therapeutic targets

et al. 2000

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ALDH1A3 promotes invasion and metastasis in triple‐negative breast cancer by regulating the plasminogen activation pathway

Bharadwaj,

McLean,

Dahn

et al. 2023

Molecular Oncology

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Aldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell marker that promotes metastasis. Triple‐negative breast cancer (TNBC) progression has been linked to ALDH1A3‐induced gene expression changes. To investigate the mechanism of ALDH1A3‐mediated breast cancer metastasis, we assessed the effect of ALDH1A3 on the expression of proteases and the regulators of proteases that degrade the extracellular matrix, a process that is essential for invasion and metastasis. This revealed that ALDH1A3 regulates the plasminogen activation pathway; it increased the levels and activity of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). This resulted in a corresponding increase in the activity of serine protease plasmin, the enzymatic product of tPA and uPA. The ALDH1A3 product all‐trans‐retinoic acid similarly increased tPA and plasmin activity. The increased invasion of TNBC cells by ALDH1A3 was plasminogen‐dependent. In patient tumours, ALDH1A3 and tPA are co‐expressed and their combined expression correlated with the TNBC subtype, high tumour grade and recurrent metastatic disease. Knockdown of tPA in TNBC cells inhibited plasmin generation and lymph node metastasis. These results identify the ALDH1A3–tPA–plasmin axis as a key contributor to breast cancer progression.

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Increased plasminogen binding is associated with metastatic breast cancer cells: differential expression of plasminogen binding proteins

Cited by 61 publications

References 37 publications

The topology of plasminogen binding and activation on the surface of human breast cancer cells

The topology of plasminogen binding and activation on the surface of human breast cancer cells

Urokinase-type plasminogen activator and its receptor in colorectal cancer: Independent prognostic factors of metastasis and cancer-specific survival and potential therapeutic targets

ALDH1A3 promotes invasion and metastasis in triple‐negative breast cancer by regulating the plasminogen activation pathway

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