Endothelial cells and normal breast epithelial cells enhance invasion of breast carcinoma cells by CXCR-4-dependent up-regulation of urokinase-type plasminogen activator receptor (uPAR, CD87) expression
Autor: | Francesco Liotta, Luigi Minafra, Marco Pucci, M. Del Rosso, Ida Pucci-Minafra, Gabriella Fibbi, Francesca Margheri, Francesco Annunziato, Simona Serratì, G Di Cara |
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Přispěvatelé: | SERRATI' S, MARGHERI F, FIBBI G, DI CARA G, MINAFRA L, PUCCI-MINAFRA I, FRANCESCO LIOTTA F, ANNUNZIATO F, PUCCI M, DEL ROSSO M |
Rok vydání: | 2008 |
Předmět: |
Receptors
CXCR4 MAP Kinase Kinase 4 Angiogenesis Cell Breast Neoplasms Receptors Cell Surface Cell Communication Biology Cell Line Receptors Urokinase Plasminogen Activator Pathology and Forensic Medicine Metastasis angiogenesis breast cancer Tumor Cells Cultured medicine Humans Neoplasm Invasiveness Breast Settore BIO/06 - Anatomia Comparata E Citologia Phosphorylation skin and connective tissue diseases CXCR4 Settore MED/04 - Patologia Generale Neovascularization Pathologic Reverse Transcriptase Polymerase Chain Reaction Fibrinolysis Epithelial Cells CXCL12 invasion medicine.disease microenvironment Chemokine CXCL12 Neoplasm Proteins Up-Regulation Endothelial stem cell Urokinase receptor medicine.anatomical_structure Culture Media Conditioned Cancer cell Cancer research Female JNK Endothelium Vascular Breast disease SDF1 uPAR Plasminogen activator |
Zdroj: | The Journal of Pathology. 214:545-554 |
ISSN: | 1096-9896 0022-3417 |
Popis: | Here we show the increase of invasion of three breast cancer cell lines (8701-BC, MDA-MB-231 and SKBR3) upon long-term co-incubation with culture medium of normal microvascular endothelial cells (MVEC) and normal breast epithelial cells (HB2). The enhancement of invasion relied on the interaction of microvascular endothelial cell and normal breast epithelial cell CXCL12 (SDF1) chemokine, whose expression by breast cancer cells was very low, with the cognate CXCR4 receptor of malignant cells, which resulted in over-expression of the urokinase-type plasminogen activator receptor (uPAR) on their surfaces. uPAR over-expression, showed by RT-PCR and Western blotting, was paralleled by increased urokinase-type plasminogen activator (uPA) partitioning on the cell surface with respect to the fluid phase, as demonstrated by zymography. Long-term interaction of SDF1 with CXCR4 stimulated sustained activation of JNK phosphorylation. Blocking antibodies to CXCR4 were able to block the endothelial/epithelial cell-dependent enhancement of invasion, as well as to inhibit SDF1-CXCR4-dependent JNK phosphorylation and uPAR over-expression of malignant cells. We suggest that acquisition of the angiogenic phenotype by breast cancer cells triggers an amplification loop, in which endothelial cells and normal breast epithelial cells of the tumour cooperate to provide facilitated routes to cell invasion and metastasis and to enhance the aggressive phenotype of cancer cells. Copyright (c) 2008 Pathological Society of Great Britain and Ireland |
Databáze: | OpenAIRE |
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