Characterization and use of in vitro and in vivo models of prostate cancer

Karen Kay Cornell, Purdue University

Abstract

Spontaneous canine prostate carcinoma is a disease of aged sexually intact dogs and dogs castrated after sexual maturity. Most common metastatic sites were regional lymph node, lung, and bone. Histopathologic classification was most commonly adenocarcinoma or tumor of mixed morphologic characteristics. Both subsets exhibited aggressive biologic behavior. Neuter status did not significantly influence morphologic subtype or biologic behavior of spontaneous canine prostate carcinoma. Canine prostate cancer cell lines (GN-4, TR5P, TR6LM, and CF-3) were characterized by brief in vitro doubling time, aneuploidy, and cytokeratin and vimentin expression. Cytokeratin and vimentin analysis were consistent with dedifferentiation of epithelial cells following malignant transformation. Conjugated linoleic acid differentially inhibited the in vitro proliferation of canine prostate cancer cells. Conjugated linoleic acid had the most profound inhibition of proliferation of GN-4 canine cell line. The apoptotic index in GN-4 and TR5P cells in culture with conjugated linoleic acid were increased which correlated directly with inhibition of proliferation seen in vitro. GN-4 cell line resulted in the most consistent colonization of bone after left ventricular injection. Time interval from injection to the development of bone colonies was 24 days. A radiographic scoring system was developed to assess extent of bone colonization after left ventricular injection of prostate cancer cells. Fatty acid composition in the skeletal and non-skeletal tissues of athymic mice was modulated by dietary conjugated linoleic acid and eicosonoid precursors were decreased significantly when fatty acid composition of bone was evaluated in a weight based analysis. Dietary conjugated linoleic acid (1%) did not inhibit the subcutaneous tumor growth of GN-4 canine prostate cancer cells in athymic mice. Subcutaneous tumor volumes were not different between mice fed 1% conjugated linoleic acid and mice fed soybean oil and there was no difference in prevalence of lung metastasis within these dietary groups. Dietary conjugated linoleic acid showed no protective effect against bone colonization following left ventricular injection of GN-4 canine prostate cells. Athymic mice fed 1% conjugated linoleic acid developed bone colonization in 100% of mice injected with GN-4 cells. Conjugated linoleic acid fed mice had increased frequency of bone colonization, extent and severity of bone lesions.

Degree

Ph.D.

Advisors

Waters, Purdue University.

Subject Area

Veterinary services|Animal diseases

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