Inhibition of stromal PlGF suppresses the growth of prostate cancer xenografts

The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the vasc...

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Bibliographic Details
Published in:International journal of molecular sciences 2013-09, Vol.14 (9), p.17958-17971
Main Authors: Zins, Karin, Thomas, Anita, Lucas, Trevor, Sioud, Mouldy, Aharinejad, Seyedhossein, Abraham, Dietmar
Format: Article
Language:English
Subjects:
Androgens
Angiogenesis
Animals
Cancer therapies
Cell growth
Cell Line, Tumor
Cell Proliferation
Fibroblasts
Humans
Kinases
Male
Mice
Placenta Growth Factor
placental growth factor
Pregnancy Proteins - genetics
Pregnancy Proteins - metabolism
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - therapy
RNA, Small Interfering - genetics
RNA, Small Interfering - physiology
Stromal Cells - metabolism
tumor angiogenesis
tumor-host interaction
Tumors
Vascular endothelial growth factor
xenograft model
Xenograft Model Antitumor Assays
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Summary:The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the vascular endothelial growth factor (VEGF) family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms140917958