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.