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
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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