Co-Expression of Urokinase With Haptoglobin in Human Carcinomas

Harvey, Shashikumar; Kohga, Shin; Sait, Sheila N.J.; Markus, Gabor; Hurd, Thelma C.; Martinick, Maisie; Geradts, Joseph; Saxena, Rakhee; Gibbs, John F.

doi:10.1016/j.jss.2008.06.016

« Previous Next »Journal of Surgical Research
Volume 152, Issue 2 , Pages 189-197, April 2009

Co-Expression of Urokinase With Haptoglobin in Human Carcinomas

Shashikumar Harvey, Ph.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
Shin Kohga, M.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
Sheila N.J. Sait, Ph.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
Gabor Markus, Ph.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
Thelma C. Hurd, M.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Surgical Oncology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
Maisie Martinick, B.S.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Surgical Oncology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
Joseph Geradts, M.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
Rakhee Saxena, M.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
John F. Gibbs, M.D.
- Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Biochemistry, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- Department of Surgical Oncology, Roswell Park Cancer Institute and State University of New York at Buffalo, Buffalo, New York
- To whom correspondence and reprint requests should be addressed at Department of GI Surgery and Endoscopy, Roswell Park Cancer Institute, Buffalo, NY 14263

Received 6 February 2007 published online 16 July 2008.

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 β-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.

Materials and 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.

Key Words: tumor markers, immunohistochemistry, FISH, urokinase, haptoglobin