Cathepsin D Activity in Human Ovarian Tissues and Ovarian Carcinoma

Abstract

OBJECTIVE: This study determined levels of cathepsin D activity in tissue components of normal human ovary to establish a basis for comparison with human ovarian adenocarcinomas.

METHODS: Cathepsin D activity per mg tissue, per μg protein, and per μg DNA was determined in human ovarian tissues (cortex, follicle, corpus luteum, corpus albicans) from patients of various ages and during the menstrual cycle. Levels of cathepsin D activity were also determined in ovarian adenocarcinomas and other pathologic tissues.

RESULTS: Cathepsin D levels (per mg tissue) were significantly greater (P < .001) in ovarian follicle and corpus luteum compared with cortex. Although there was not a clear correlation between enzyme activity in the cortex and day of the menstrual cycle or patient age, levels of enzyme activity appeared to decrease with each parameter. Cathepsin D levels per mg tissue in ovarian adenocarcinoma were 40% higher than in postmenopausal ovarian cortex, but the differ ence was not statistically significant.

CONCLUSION: The diversity of cathepsin D levels in normal ovarian tissue compartments indicates that specific tissues must be used in comparisons with ovarian tumors. (J Soc Gynecol Invest 1994;1:173-7)

Keywords

Cathepsin D normal ovarian tissue ovarian carcinoma.

Get full access to this article

View all access options for this article.

References

Berek JS Practical gynecologic oncology. Baltimore: Williams and Wilkins, 1989:327-90.

Liotta LA Gene products which play a role in cancer invasion and metastasis . Breast Cancer Research and Treatment 1988 ;11:113-24.

Ossowski L. , Biegel D. , Reich E. Mammary plasminogen activator: Correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Cell 1979;16:929-40.

Brule F. , EngelJ, Stetler W, Liu F, Sobel M. Genes involved in tumor invasion . Int J Cancer 1992;52:653-7.

Leto G. , Gebbia N. , Rausa L. , Tumminello FM Cathepsin D in the malignant progression of neoplastic diseases (Review) . Anticancer Research 1992;12:235-40.

Astedt B. , Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature 1976;261:595-6.

Astedt B. , Svanberg L. , Nilsson IM Fibrin degradation products and ovarian tumours. Br Med J 1971;4:458-9.

Kanemoto T. , Martin GR , Hamilton TC , Fridman R. Effects of synthetic peptides and protease inhibitors on the interaction of a human ovarian cancer cell line (NIH: OVCAR-3) with a reconstituted basement membrane (Matrigel). Invasion Metastasis 1991 ;11:84-92.

Spyratos F. , Brouillet JP , Defrenne A. , et al. Cathepsin D: An independent prognostic factor for metastasis of breast cancer. Lancet 1989;8672:1115-8.

10.

Tandon AK , Clark GM , Chamness GC , Chirgwin JM , McGuire WL Cathepsin D and prognosis in breast cancer. N Engl J Med 1990;322:297-302.

11.

Scambia G. , Benedetti P. , Ferrandina G. , Battaglia F. , Baiocchi G. , Mancuso S. Cathepsin D assay in ovarian cancer: Correlation with pathological features and receptors for oestrogen, progesterone and epidermal growth factor . Br J Cancer 1991;64:182-4.

12.

Dhanasekaran N. , Moudgal NR Studies on follicular atresia: Role of tropic hormone and steroids in regulating cathepsin-D activity of preantral follicles of the immature rat. Mol Cell Endocrinol 1986 ;44:77-84.

13.

Lahav M. , Meidan R. , Amsterdam A. , Gebauer H. , Lindner HR Intracellular distribution of cathepsin D in rat corpora lutea in relation to reproductive state and the action of prostaglandin F2α and prolactin. J Endocrinol 1977;75:317-24.

14.

Sensibar JA , Liu X. , Patai B. , Alger B. , Lee C. Characterization of castration-induced cell death in the rat prostate by immunohistochemical localization of cathepsin D. Prostate 1990 ;16:263-76.

15.

Elangovan S. , Moulton BC Blastocyst implantation in the rat and the immunohistochemical distribution and rate of synthesis of uterine lysosomal cathepsin D. Biol Reprod 1981;23:663-76.

16.

Briozzo P. , Morisset M. , Capony F. , Rougeot C. , Rochefort H. In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells. Cancer Res 1988;48:3688-92.

17.

Leto G. , Tumminello FM , Gebbia N. Woyrnarowska B , Bernacki RJ Antimetastatic effects of adriamycin in combination with proteinase inhibitors . Anticancer Res 1990; 10:265-70.

18.

Mathieu M. , Rochefort H. , Barenton B. , Prebois C. , Vignon F. Interaction of cathepsin D and insulin-like growth factor II (IGF-II) on the IGF-II/mannose-6-phosphate receptor in human breast cancer cells and possible consequence on mitogenic activity of IGF-II. Mol Endocrinol 1990;4:1327-35.

19.

Greenbaum LM , Grebow P. , Johnston M. , Prakash A. , Semente G. Pepstatin, an inhibitor of leukokinin formation and ascitic fluid accumulation . Cancer Res 1975;35:706-10.

20.

Greenbaum LM , Semente G. Pepstatin as ascites retardant of L1210 tumor bearing mice. J Natl Cancer Inst 1977;59: 259-62.

21.

Morisset M. , Capony F. , Rochefort H. Processing and estrogen regulation of the 52-kilodalton protein inside MCF7 breast cancer cells. Endocrinology 1986;119:2773-82.

22.

Moulton BC , Koenig BB Progestin increases cathepsin D synthesis in uterine luminal epithelial cells . Am J Physiol 1983;244:E442-6.