A novel immunological model for the study of prostate cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 10; pp. 2271 - 2276
• Main Authors: SHARMA, N, JUN LUO, KIRSCHMANN, D. A, O'MALLEY, Y, ROBBINS, M. E. C, AKPORIAYE, E. T, LUBAROFF, D. M, HEIDGER, P. M, HENDRIX, M. J. C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.05.1999
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - pathology; Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Cell Separation - methods; Chemotaxis, Leukocyte; Experimental renal and urinary tract tumors; Flow Cytometry; Interleukin-10 - secretion; Leukocyte Count; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Lymphocytes, Tumor-Infiltrating - secretion; Male; Medical sciences; Microscopy, Electron, Scanning; Neoplasm Metastasis; Neoplasm Transplantation - instrumentation; Neoplasm Transplantation - methods; Phenotype; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Prostheses and Implants; Rats; Surgical Sponges; Transforming Growth Factor beta - secretion; Tumors; Adenocarcinoma; Animal model; Urinary system disease; Prostate disease; Rat; Transforming growth factor β; Immunomodulation; Gene product; Cytokine; Rodentia; Malignant tumor; Gene expression; In vitro; In vivo; Vertebrata; Mammalia; Animal; Interleukin 10; Established cell line; Tumor progression; Male genital diseases; Prostate; Tumor cell
• ISSN: 0008-5472; 1538-7445

The Dunning R-3327 rat prostatic adenocarcinoma is a widely accepted model for in vivo experimental studies of prostate cancer. We have previously derived phenotypically distinct cell lines from a s.c. tumor resulting from the inoculation of the R-3327-5 subclone into Copenhagen rats. In this study, we report studies using a gelatin sponge model for the delivery of tumor cells and the retrieval of tumor-specific leukocytes responsive to different prostatic cell lines. S.c. preimplanted sponges were inoculated with tumor cells previously selected for differential properties of tumor formation and metastasis and examined for leukocyte content at time points of 1, 3, and 5 weeks after tumor cell inoculation. Cytospin and flow cytometric analyses revealed fewer tumor-associated leukocytes present in sponges inoculated with tumorigenic R-3327-5' and R-3327-5'B lines, with lesser sponge degradation, than in experiments with the nontumorigenic R-3327-5'A line, suggestive of a tumor cell-induced immunomodulatory mechanism. Morphological studies indicate an intermittent tumor growth pattern that gradually disappears in sponges inoculated with the nontumorigenic R-3327-5'A cells but a robust growth pattern in sponges inoculated with the tumorigenic cell lines. Cytokine analyses show the secretion of higher levels of active transforming growth factor-beta by the more invasive and metastatic lines. Total transforming growth factor-beta levels are higher in the epithelial, tumorigenic R-3327-5'B line. Additionally, the more tumorigenic lines secrete interleukin 10, a potent immunosuppressive molecule. In this report, we demonstrate the ability to retrieve viable leukocyte populations from a prostate tumor line bearing sponges, which offers an important model for further in vitro and in vivo manipulations and holds promise for testing adoptive immunotherapeutic strategies.