Adenoviral-Mediated Endothelial Precursor Cell Delivery of Soluble CD115 Suppresses Human Prostate Cancer Xenograft Growth in Mice

Abstract

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.

Pattern of invasion of the embryonic mouse spinal cord by microglial cells at the time of the onset of functional neuronal networks

“…von Willebrand Factor (vWF) antibody ab6994 was used to visualize developing blood vessels (Curry et al, 2008;Lucas et al, 2009). Immunostaining using ab6994 antibody reveals the spinal cord growing blood capillaries (Fig.…”

PlGF and VEGF-A Regulate Growth of High-Risk MYCN-Single Copy Neuroblastoma Xenografts via Different Mechanisms

“…The 2289 bp construct was gel purified with Qiaex II (Qiagen, Valencia, CA, USA) and recombinant adenovirus Ad(s)VEGFR2 was constructed as described [45]. Adeno-X-DSRed2 adenovirus for expressing red fluorescent protein (AdRFP) was obtained from Clontech and propogated in HEK293 culture.…”

Adult and Pluripotent Stem Cells

“…Furthermore, the soluble CD115 secreted by the cells obviously blocked the activation of macrophages in the tumor environment and thus suppressed the growth of the prostate tumor (Lucas et al 2009). When we transduced ECFCs with an adenovirus to secrete a soluble form of colony stimulating factor-1 receptor (CD115) that inhibits macrophage viability and migration, and injected these cells into a prostate tumor xenograft model, homing of the cells to regions of ischemia in the growing tumors was observed.…”