Adipose Tissue-Derived Stem Cells Promote Prostate Tumor Growth

BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSION. 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. Prostate 70: 1709-1715, 2010. (C) 2010 Wiley-Liss, Inc.