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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
uPA and PAI-1-related signaling pathways differ between primary breast cancers and lymph node metastases.
Transl. Oncol. 5, 98-104 (2012)
The supporting role of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) in migration and invasion is well known. In addition, both factors are key components in cancer cell-related signaling. However, little information is available for uPA and PAI-1-associated signaling pathways in primary cancers and corresponding lymph node metastases. The aim of this study was to compare the expression of uPA and PAI-1-associated signaling proteins in 52 primary breast cancers and corresponding metastases. Proteins were extracted from formalin-fixed paraffin-embedded tissue samples of the primary tumors and metastases. Protein lysates were subsequently analyzed by reverse phase protein array for the expression of members of the PI3K/AKT (FAK, GSK3-β, ILK, pGSK3-β, PI3K, and ROCK) and the MAPK pathways (pp38, pSTAT3, and p38). A solid correlation of uPA expression existed between primary tumors and metastases, whereas PAI-1 expression did not significantly correlate between them. The correlations of uPA and PAI-1 with signaling pathways found in primary tumors did not persist in metastases. Analysis of single molecules revealed that some correlated well between tumors and metastases (FAK, pGSK3-β, ILK, Met, PI3K, ROCK, uPA, p38, and pp38), whereas others did not (PAI-1 and GSK3-β). Whether the expression of a protein correlated between tumor and metastasis or not was independent of the pathway the protein is related to. These findings hint at a complete deregulation of uPA and PAI-1-related signaling in metastases, which might be the reason why uPA and PAI-1 reached clinical relevance only for lymph node-negative breast cancer tissues.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
PLASMINOGEN-ACTIVATOR INHIBITOR-1; PHASE PROTEIN ARRAYS; UROKINASE-TYPE; P38 MAPK; MICROARRAY ANALYSIS; ENDOTHELIAL-CELLS; E-CADHERIN; C-JUN; EXPRESSION; KINASE
e-ISSN
1936-5233
Zeitschrift
Translational Oncology
Quellenangaben
Band: 5,
Heft: 2,
Seiten: 98-104
Verlag
Neoplasia Press
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed