Adenoviral-mediated endothelial precursor cell delivery of soluble CD115 suppresses human prostate cancer xenograft growth in mice.
Prostate cancer tumor growth and neovascularization is promoted by an interplay between migratory tumor stromal cells such as specialized tumor-associated macrophages (TAMs) and circulating endothelial precursor cells (CEPs). As vehicles for tumor therapy, human CEPs are relatively easy to isolate from peripheral blood, are able to proliferate long-term in vitro, are amenable to viral manipulation, and preferentially home to regions of ischemia found in growing tumors. We show here that human peripheral blood CEPs expanded ex vivo migrate to prostate cancer cells in vitro and efficiently home to human prostate tumor xenografts in vivo. Infection of precursors ex vivo with an adenovirus constructed to secrete a soluble form of the colony-stimulating factor-1 receptor CD115 that inhibits macrophage viability and migration in vitro significantly decreases the number of TAMs in xenografts (p < .05), reduces proliferation (p < .01) and vascular density (p < .03), and suppresses the growth of xenografts (p < .03). These data show for the first time that targeting stromal cell processes with cellular therapy has the potential to retard prostate tumor growth.
Lucas
Trevor
T
Laboratory for Cardiovascular Research, Department of Anatomy and Cell Biology, Vienna Medical University, Vienna, Austria.
Abraham
Dietmar
D
Untergasser
Gerold
G
Zins
Karin
K
Hofer
Erhard
E
Gunsilius
Eberhard
E
Aharinejad
Seyedhossein
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation / Q000379:methods; D023041:Xenograft Model Antitumor Assays
D016186:Receptor, Macrophage Colony-Stimulating Factor