Kocheril S V, Grignon D J, Wang C Y, Maughan R L, Montecillo E J, Talati B, Tekyi-Mensah S, Pontes J e, Hillman G G
Department of Urology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Cancer Detect Prev. 1999;23(5):408-16. doi: 10.1046/j.1525-1500.1999.99039.x.
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 heterotransplanted 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.
我们使用骨肿瘤模型测试了一种免疫疗法用于治疗转移性前列腺癌。将人PC-3前列腺癌细胞异种移植到无胸腺Balb/c裸鼠的股骨腔内。肿瘤细胞取代了骨腔内的骨髓细胞，侵入相邻的骨和肌肉组织，并在髋关节处形成可触及的肿瘤。通过体内连续传代从骨肿瘤产生的PC-3/IF细胞系在股骨中生长动力学更快，并转移至腹股沟淋巴结。对已形成的肿瘤进行全身注射白细胞介素-2（IL-2）治疗。IL-2在无毒低剂量时显著抑制可触及肿瘤的形成并延长小鼠存活时间。组织学上，IL-2导致肿瘤内血管损伤、多形核细胞和淋巴细胞浸润以及伴有凋亡细胞的坏死区域。这些发现提示全身IL-2治疗可破坏肿瘤细胞以及前列腺癌骨肿瘤对IL-2有反应性。
