Protein and mRNA expression of uPAR and PAI-1 in myoepithelial cells of early breast cancer lesions and normal breast tissue
| Autor: | N Arens, R Hildenbrand |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Cancer Research Pathology medicine.medical_specialty Serine Proteinase Inhibitors DCIS Mammary gland PAI-1 Breast Neoplasms Receptors Cell Surface Biology myoepithelial cells Metastasis Receptors Urokinase Plasminogen Activator Extracellular matrix chemistry.chemical_compound Plasminogen Activators Antigens CD Plasminogen Activator Inhibitor 1 medicine Humans RNA Messenger skin and connective tissue diseases neoplasms Aged Enzyme Precursors Myoepithelial cell Molecular and Cellular Pathology Ductal carcinoma Middle Aged medicine.disease Urokinase-Type Plasminogen Activator Urokinase receptor medicine.anatomical_structure Carcinoma Intraductal Noninfiltrating Oncology chemistry Plasminogen activator inhibitor-1 biology.protein Vitronectin Female uPAR |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Myoepithelial cells (MEs), which surround ducts and acini of the breast glands, exhibit an anti-invasive phenotype and form a natural border separating proliferating tumour cells of ductal carcinoma in situ (DCIS) from basement membrane (bm) and underlying stroma. Invasion requires penetration of these host cellular and extracellular matrix barriers. This destruction is caused by proteolytic activity of tumour cells and host bystander cells. There is substantial evidence that high concentrations of the urokinase plasminogen-activating system are conducive to tumour cell spread and metastasis. Prompted by the conspicuous absence of studies examining the role of the ME in breast cancer progression, we studied the expression of the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor type-1 (PAI-1) in MEs of 60 DCIS samples. Our results show that nearly all MEs of DCIS and normal breast glands exhibit the uPAR antigen, whereas the PAI-1 antigen was mainly expressed in MEs of high-grade DCIS. In one intermediate DCIS numerous ducts showed an incomplete myoepithelial layer expressing uPAR and PAI-1. We conclude that uPAR in MEs may be necessary to attach them to the bm by uPAR/vitronectin (Vn) interaction. The strong expression of PAI-1, which is known to resolve the uPAR/Vn binding, may be involved in the detachment of MEs of DCIS. Although the role of PAI-1 acting as cell detachment factor could not be demonstrated in our study, we speculate that the loss of the anti-invasive ME layer in DCIS may be triggered by PAI-1 and could be an early sign of subsequent tumour cell infiltration. |
| Databáze: | OpenAIRE |
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