Reduced Growth, Increased Vascular Area, and Reduced Response to Cisplatin in CD13-Overexpressing Human Ovarian Cancer Xenografts

• Published in: Clinical cancer research 2004-02, Vol.10 (3), p.1180-1191
• Main Authors: VAN HENSBERGEN, Yvette, BROXTERMAN, Henk J, RANA, Sareena, VAN DIEST, Paul J, DUYNDAM, Monique C. A, HOEKMAN, Klaas, PINEDO, Herbert M, BOVEN, Epie
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Mucinous - metabolism; Aminopeptidases - metabolism; Animals; Antineoplastic agents; Apoptosis; Biological and medical sciences; CD13 Antigens - biosynthesis; Cell Adhesion; Cell Division; Cell Line, Tumor; Cell Membrane - metabolism; Cisplatin - pharmacology; Collagen - pharmacology; Cystadenocarcinoma, Serous - metabolism; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Immunohistochemistry; Laminin - pharmacology; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Pharmacology. Drug treatments; Plasmids - metabolism; Proteoglycans - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; S Phase; Time Factors; Transfection; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-0482-3

Purpose: Expression of aminopeptidase N/CD13 can be detected in several solid tumor types. Thus far, the role of CD13 in ovarian cancer has not been studied. We have investigated the expression pattern and biological function of CD13 in ovarian cancer. Experimental Design: First, we studied the expression of CD13 in ovarian cancer tissue of 15 patients representing three different histological types (5 patients each) by immunohistochemistry. We then stably transfected the IGROV-1 human ovarian cancer cell line with a CD13 expression vector and examined the biological effect of CD13 in vitro and in vivo . Results: The expression of CD13 in ovarian cancer was associated with the histological subtype: CD13 expression in tumor cells was observed in 80–100% of the patients with a serous or mucinous carcinoma and in only 20% of the clear cell carcinoma patients. In all patients’ tumor samples, CD13-positive blood vessels were present. CD13 overexpression in IGROV-1 cells did not affect in vitro cell growth and sensitivity to doxorubicin, cisplatin, or gemcitabine. CD13 overexpression reduced invasion in Matrigel, which appeared to be independent of the aminopeptidase activity of CD13. Furthermore, the growth rate of IGROV-1/CD13 xenografts was reduced. The area of the vessel lumens was enlarged in a small percentage of vessels in the CD13-overexpressing xenografts. In addition, the CD13-overexpressing tumors were less sensitive to cisplatin. Conclusions: CD13 is expressed in tumor as well as endothelial cells in human ovarian cancer. Our results suggest that CD13 overexpression affects ovarian cancer growth, vascular architecture, and response to chemotherapy. Further elucidation of the mechanism of the observed effects of CD13 is warranted to better understand its role in the pathophysiology of ovarian cancer.