Co-expression of urinary plasminogen activator and haptoglobin in human colon and breast tumors evaluated by immunocytochemistry, in situ hybridization and molecular analysis

S. R. Harvey, S. Kohga, T. Hurd, Saits, G. Markus

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Considerable evidence has accumulated to show that urinary plasminogen activator (uPA) plays a key role in tumor progression and metastasis. We have recently shown that a low M uPA (21 kDa) is secreted as a covalent complex with haptoglobin (Hp) and a neural cell adhesion-like molecule (NCAM).' We postulated that the NCAM portion of the complex is required for the focalization of uPA at the extracellular matrix while the Hp portion is involved in immunosuppression. We have therefore investigated to see whether uPA, Hp, and NCAM co-localized in the tumor cells. Immunofluorescent staining of cultured colon and breast tumor cell lines with monoclonal antibodies to uPA, NCAM and rabbit polyclonal anti-Hp showed cell surface staining that co-localized with all the three ami-bodies. These studies were extended to paraffin embedded sections of 12 colon and 12 invasive breast tumors using the biotin-avidin-HRP system in a Ventana automated stainer. In all tumors investigated anti-NCAM gave little (1+) or no staining unlike that observed with cultured tumor cells. Normal colon and breast tissue showed no staining with anti-uPA or anti-Hp. All tumors stained for uPA that localized both in the cytoplasm and in the membrane. Some colon tumors showed intra-cytoplasmic uPA location in granular form in basal, apical and in the mid portions of cancer cells along with intraluminal debris of tubular structures of cancer. Only occasional staining of uPA in the strorna around the colon tumors was observed. The breast tumor sections revealed heterogeneous staining for uPA with patterns ranging from weak to diffuse and strong, the latter being at the invasive growth of the tumors. Anti-Hp on the other hand stained 18/24 tumor sections. This staining was intense in many cases and appears to be similar to that seen with anti-uPA. However, the antiHp also stained the desmoplastic and edematous area in the stroma which we attribute to inflammatory cells like histiocytes and neutrophils. FISH with uPA cDNA and Hp a-cDNA showed that uPA and Hp mRNA are localized in the tumor cells with little or no signal in the stroma. PC R analysis of tumor cells has shown abundant expression of both uPA and Hp gene complex that includes the Hp related genes. These results indeed establish that the uPA-NCAM-Hp complex is expressed by tumor cells.

Original languageEnglish (US)
Number of pages1
JournalFibrinolysis and Proteolysis
Issue numberSUPPL. 1
StatePublished - Dec 1 2000


ASJC Scopus subject areas

  • Hematology

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