title: Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth.
abstract: BACKGROUND
  Recent reports have linked the survival-promoting effect of CXCR4 to the up regulation of Bcl-2 protein expression.
  
  
  METHODS
  To further elucidate the relationship between Bcl-2 and CXCR4, tumorigenicity was evaluated in in vitro and in vivo models following treatment with CTCE-9908, a CXCR4 antagonist peptide.
  
  
  RESULTS
  In vitro, CTCE-9908 inhibited cellular proliferation in PC-3-Bcl-2 and PC-3-Neo cell lines Furthermore in our xenograft model, CTCE-9908 delivered via daily intraperitoneal injections resulted in a statistically significant reduction in tumor size compared to control (396 + 205 mm(3) vs. 1,010 + 215 mm(3) respectively, p < 0.05) in the Bcl-2 expressing tumors. This reduction was associated with knockdown of VEGF, inhibition of angiogenesis and lymphangiogenesis, and induction of apoptosis. CTCE-9908 therapy was also associated with a marked reduction in intra-tumoral host cells expressing VEGFR1 and CD11b myeloid-derived suppressor cells (MDSC).
  
  
  CONCLUSIONS
  These data show that CXCR4 antagonists represent a valuable addition to the cancer therapeutic arsenal. Such agents may have beneficial synergistic dual-effects in reducing tumor cell proliferation directly, and indirectly through perturbation of the tumor microenvironment. Further studies of the novel CTCE-9908 compound in prostate and other solid tumor inhibition are warranted. Prostate 69: 1460-1469, 2009. (c) 2009 Wiley-Liss, Inc.
authors: Department of Urology, University of Florida, Gainesville, Florida, USA.
authors: Stacy
authors: S
authors: Porvasnik
authors: Noboru
authors: N
authors: Sakamoto
authors: Sergei
authors: S
authors: Kusmartsev
authors: Evgeniy
authors: E
authors: Eruslanov
authors: Wan-Ju
authors: WJ
authors: Kim
authors: Wengang
authors: W
authors: Cao
authors: Cydney
authors: C
authors: Urbanek
authors: Donald
authors: D
authors: Wong
authors: Steve
authors: S
authors: Goodison
authors: Charles J
authors: CJ
authors: Rosser
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D039481:CD11b Antigen / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D039481:CD11b Antigen; C540323:CTCE-9908; C527276:CXCR4 protein, human; D010455:Peptides; D019718:Receptors, CXCR4; D040281:Vascular Endothelial Growth Factor Receptor-1; D051057:Proto-Oncogene Proteins c-akt