Published in Cancer Detection and Prevention 1999; 23(5):408-416.

Responsiveness of Human Prostate Carcinoma Bone Tumors to Interleukin-2 Therapy in a Mouse Xenograft Tumor Model

Sosa V. Kocheril, M.D.,a David J. Grignon, M.D.,b Ching Y. Wang, Ph.D.,c Richard L. Maughan, Ph.D.,d Emily J. Montecillo, B.Sc.,a Bharat Talati, M.Sc.,a Samuel Tekyi-Mensah, Ph.D.,d J. Edson Pontes, M.D.,a and Gilda G. Hillman, Ph.D.a,d

Departments of a Urology, b Pathology and d Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine and Harper Hospital, Detroit, Michigan, and the c Department of Urology, State University of New York Health Science Center, Syracuse, New York

Address all correspondence and reprint requests to: G. G. Hillman, Ph.D., Department of Radiation Oncology. Wayne State University School of Medicine, Rm. 150 Lande Bldg., 550 E. Canfield St., Detroit, MI 48201,

ABSTRACT: We have tested an immunotherapy approach for the treatment of metastatic prostate carcinoma using a bone tumor model. Human PC-3 prostate carcinoma tumor cells were heterotranspianted into the femur cavity of athymic Balb/c nude mice. Tumor cells replaced marrow cells in the bone cavity, invaded adjacent bone and muscle tissues, and formed a palpable tumor at the hip joint. PC-3/IF cell lines, generated from bone tumors by serial in vivo passages, grew with faster kinetics in the femur and metastasized to inguinal lymph nodes. Established tumors were treated with systemic interleukin-2 (IL-2) injections. IL-2 significantly inhibited the formation of palpable tumors and prolonged mouse survival at nontoxic low doses. Histologically IL-2 caused vascular damage and infiltration of polymorphonuclear cells and lymphocytes in the tumor as well as necrotic areas with apoptotic cells. These findings suggest destruction of tumor cells by systemic IL-2 therapy and IL-2 responsiveness of prostate carcinoma bone tumors.

KEY WORDS: bone tumors, immunotherapy, prostate carcinoma.

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