Search

Background. Estrogen receptor (ER) has been found in human pancreatic carcinoma, but the potential benefit of endocrine therapy never has been assessed adequately. The aim of this study was to determine whether the presence of ER can be used as an indicator of hormone responsiveness, and whether modulation of tissue-type plasminogen activator (t-PA) by ER can identify hormone-responsive pancreatic carcinomas. Methods. The authors investigated ER status and hormonal regulation of t-PA in nine human pancreatic carcinoma cell lines, AsPC-1, BxPC-3, Capan-1, Capan-2, Hs-700T, Hs-766T, MiaPaCa-2, PANC-1, and SUIT-2. Furthermore, to examine whether estrogen dependency of t-PA production in pancreatic carcinoma cells correlated with responsiveness to endocrine therapy, the in vivo effects of various endocrine agents on the growth of the nine pancreatic cell lines transplanted into nude mice were examined. Results. In a 17beta-estradiol ([E.sub.2])-binding assay, three of the nine pancreatic carcinoma cell lines (BxPC-3, Capan-2, and MiaPaCa-2) contained measurable levels of estradiol binding sites in vitro and in vivo using tumors transplanted into nude mice. Although t-PA was present in the culture medium in eight of the nine pancreatic carcinoma cell lines (not in Hs-700T), t-PA production was regulated by estrogen via an ER system in vitro only in the Capan-2 cell line. [E.sub.2] injection into tumor-bearing mice showed acceleration of tumor growth only in Capan-2 tumors. Administration of a competitive ER antagonist, toremifene, and a luteinizing hormone-releasing hormone analogue, leuprorelin acetate (LEU), to Capan-bearing 2-mice significantly reduced the rate of tumor growth, although there was no actual shrinkage of tumor mass. These agents failed to exert any antitumor effect on the other eight pancreatic cell lines. Although aromatase inhibitors, CGS 20267 and vorozole did not modify the in vivo growth of the nine pancreatic carcinoma cell lines significantly, the combined use of aromatase inhibitors with LEU exhibited a synergistic antitumor effect on Capan-2-bearing mice. Medroxyprogesterone acetate treatment significantly reduced the tumor volume of Capan-2 and also caused delayed growth in two other cell lines, AsPC-1 and MiaPaCa-2. Conclusions. The estrogen dependency of t-PA production may clarify the functional state of ER in human pancreatic carcinoma cells. This finding may aid in planning endocrine therapy for patients with this lethal cancer. Cancer 1995;75:1263-72.

Background. Recently, the authors reported that membrane-associated phospholipase [A.sub.2] (M-[PLA.sub.2]) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. Methods. M-[PLA.sub.2] concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. Results. Tissue levels of M-[PLA.sub.2] concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-[PLA.sub.2] and clinicopathologic factors showed that tissue M-[PLA.sub.2] levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-[PLA.sub.2] concentration and steroid hormone receptor status. Immunohistochemically, M-[PLA.sub.2] was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-[PLA.sub.2] showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-[PLA.sub.] concentration could be a powerful prognostic factor in predicting such survival rates. Conclusions. M-[PLA.sub.2] is closely related to the malignant potential of breast cancers, and the M-[PLA.sub.2] contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer. Cancer 1993; 71:3058-64.