Co-expression of urokinase with haptoglobin in human carcinomas.
BACKGROUND
We have shown that colon and breast cancer contains large amounts of urokinase (uPA), and that these cells are the actual sites of its synthesis. We isolated a large complex molecule consisting of the beta-chain of uPA, both chains of haptoglobin (Hp), and part or all of an NCAM-like molecule. The question arose whether it would be possible to show the presence of Hp in the same cells where uPA was found.


METHODS
Human colon and breast adenocarcinomas were investigated for expression of Hp and uPA by immunohistochemistry. Fluorescence in situ hybridization was used to identify the cells of origin of these antigens.


RESULTS
Hp was expressed in 8 of 11 colon adenocarcinomas, and in 10 of 12 breast tumors. uPA was demonstrable on the cell membrane and in the cytoplasm of all 11 colon adenocarcinomas studied, and cytoplasmic uPA-mRNA was found in all cases. While uPA was also detected in some stromal and inflammatory cells, Hp was present abundantly in such cells, as well as in capillary endothelial cells. Hp-mRNA was also found in both colon and breast tumors wherever the antigens were expressed.


CONCLUSIONS
uPA and Hp are produced by the cancer cells and are not taken up by stromal elements. While the role of uPA in the malignant process is well documented, that of Hp is largely unexplored. Its ubiquity, shown here, suggests that it is also involved in some aspects of that process.
Harvey
Shashikumar
S
Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York 14263, USA.
Kohga
Shin
S
Sait
Sheila N J
SN
Markus
Gabor
G
Hurd
Thelma C
TC
Martinick
Maisie
M
Geradts
Joseph
J
Saxena
Rakhee
R
Gibbs
John F
JF
D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012811:Sigmoid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D006242:Haptoglobins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014568:Urokinase-Type Plasminogen Activator