Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Prostate. 2010 Nov 1;70(15):1709-15. doi: 10.1002/pros.21206.
Recent evidence indicates that cancer stem cells play an important role in tumor initiation and maintenance. Additionally, the effect of tissue-resident stem cells located in the surrounding healthy tissue on tumor progression has been demonstrated. While most knowledge has been derived from studies of breast cancer cells, little is known regarding the influence of tissue resident stem cells on the tumor biology of prostate cancer.
Twenty male athymic Swiss nu/nu mice (age: 6-8 weeks) were randomized into two treatment groups: (1) subcutaneous injection of 10(6) MDA PCa 118b human prostate cancer cells into the upper back or (2) subcutaneous injection of 10(6) MDA PCa 118b cells mixed directly with 10(5) GFP-labeled human adipose tissue-derived stem cells (hASCs). Tumor growth and volumes over the ensuing 3 weeks were assessed using calipers and micro-computed tomography. Immunohistochemistry was performed to identify engrafted hASCs in tumor sections.
At 3 weeks after injection, the mean tumor volume in the MDA PCa 118b/hASC co-injection group (1019.95 ± 73.49 mm(3)) was significantly higher than that in the MDA PCa 118b-only group (308.70 ± 21.06 mm(3)). Engrafted hASCs exhibited the nuclear marker of proliferation Ki67 and expressed markers for endothelial differentiation, indicating their engraftment in tumor vessels.
Our study revealed for the first time that ASCs subcutaneously co-injected with prostate cancer cells engraft and promote tumor progression. Further evaluation of the cross-talk between tumor and local tissue-resident stem cells may lead to new strategies for prostate cancer therapy.
最近的证据表明，癌症干细胞在肿瘤的发生和维持中起着重要作用。此外，位于周围健康组织中的组织驻留干细胞对肿瘤进展的影响也已经得到证实。虽然大多数知识都是从乳腺癌细胞的研究中得出的，但对于组织驻留干细胞对前列腺癌肿瘤生物学的影响知之甚少。
将 20 只雄性无胸腺瑞士 nu/nu 小鼠（年龄：6-8 周）随机分为两组：（1）将 10（6）个 MDA PCa 118b 人前列腺癌细胞皮下注射到背部上方，或（2）将 10（6）个 MDA PCa 118b 细胞与 10（5）个 GFP 标记的人脂肪组织源性干细胞（hASC）直接混合皮下注射。用游标卡尺和微计算机断层扫描评估接下来 3 周内肿瘤的生长和体积。进行免疫组织化学以鉴定肿瘤切片中植入的 hASC。
在注射后 3 周，MDA PCa 118b/hASC 共注射组（1019.95±73.49mm3）的平均肿瘤体积明显高于 MDA PCa 118b 单独注射组（308.70±21.06mm3）。植入的 hASC 显示增殖核标记物 Ki67，并表达内皮分化标志物，表明其在肿瘤血管中植入。
我们的研究首次揭示了与前列腺癌细胞皮下共注射的 ASC 会植入并促进肿瘤进展。进一步评估肿瘤与局部组织驻留干细胞之间的相互作用可能会为前列腺癌治疗带来新的策略。
