Normal prostate‐derived stromal cells stimulate prostate cancer development

Abstract

Stromal cells play a decisive role in regulating tumor progression. In this study, we assessed the significance of normal prostate‐derived stromal cells (PSCs) in prostate cancer development. An in vivo s.c. tumor model was established as follows: Group 1, DU145 cells alone; Group 2, DU145 + PSCs; Group 3, DU145 cells alone injected into pre‐castrated mice; and Group 4, DU145 + PSCs injected into pre‐castrated mice. Following injection, tumors were only detectable in the first two groups, with more aggressive growth in Group 2 than in Group 1 (P < 0.05). Immunohistochemical analysis revealed significantly higher proliferation (P < 0.05), but not apoptosis or altered expression of androgen receptor in Group 2, as compared with Group 1. In vitro, DU145 cells isolated from Group 1 tumors showed lower viability and migratory capability than those from Group 2. cDNA microarray on isolated DU145 cells from Groups 1 and 2 revealed the differential expression of genes regulating cell cycle progression and cell mobility, including GADD45A, RHOV, KLK11, and PCK1. Our results suggest that stromal cells derived from normal prostate potentiate the development of tumor growth in vivo, which is achieved at least in part through the regulation of cell‐cycle‐ and migration‐related gene expression within the tumor cells. (Cancer Sci 2011; 102: 1630–1635)

Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma

“…Furthermore, they noted that knockdown of PCK1 reduced lactate release, slowing metabolism. In an in vivo study, mice injected with DU145 prostate cancer cells plus prostate-derived stromal cells had higher expression of PCK1 and more aggressive tumor growth than mice injected with DU145 cells alone [30]. Thus, our finding of PCK1 decrease following PLK1 knockdown samples is consistent with reported studies and suggests that an overexpression of PLK1 might play a role in upregulating PCK1, which can increase glucose metabolism and tumor growth potential.…”

Human Stromal Cells in the Peripheral Zone of the Prostate Promote Tumorigenesis of Prostatic Cancer Stem Cells through Up-regulation of C-Kit Expression

“…The isolation and culture of primary prostate stromal cells was carried out as previously described 13 . To trace normal prostate-derived stromal cells, we labeled isolated prostate stromal cells with 10µm carboxyfluorescein succinimidyl ester (CFSE) (Invitrogen, CA) from a labeling kit according to the manufacturer's instructions.…”

“…Purification of DU145 cells from the tumors of an in vivo tumorigenesis mouse model was carried out as previously described 13 .…”

“…Epithelial cells from the tumors of mice receiving cell transplantation were isolated and cultured as described previously 13 . Cells at a passage number of 6 to 10 were used for further experiments.…”

“…Zhao et al found that PC3 cells showed increased tumorigenic ability after being cultured with the stromal cells isolated from either the PZ or TZ of normal human prostates; this increased tumorigenic ability was more obvious after PC3 cells were cultured with stromal cells from the PZ than from the TZ 12 . Peng et al found that DU145 cells also showed increased ability to proliferate and migrate after being cultured with stromal cells isolated from the PZ of normal human prostates 13 . These observations suggest that stromal-epithelial interactions may regulate the stem cell properties of CSCs and, thus, alter their tumorigenic ability.…”