Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model

August 2013
Oncology Letters;2013, Vol. 6 Issue 4, p933
Academic Journal
The stromal derived factor-1 (SDF-1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in prostate cancer. The present study aimed to explore the potential therapeutic effects of a CXCR4 antagonist in prostate cancer. The effect of SDF-1 and a CXCR4-specific antagonist, AMD3100, on human prostate cancer PC-3 cell proliferation and protein kinase B (Akt) signaling was assessed. Moreover, a PC-3 tumor xenograft model was used to evaluate the effect of AMD3100 on tumor growth and to identify the histopathological changes and immunohistochemical differences between AMD3100-treated and untreated groups. Cell proliferation was not significantly affected by SDF-1 or AMD3100 treatment in vitro. Western blot analysis revealed that SDF-1 stimulation enhanced the expression of phosphorylated Akt in the PC-3 cells, but that the SDF-1-induced expression of phosphorylated Akt was abrogated in the AMD3100-treated PC-3 cells. In the PC-3 tumor xenograft model, AMD3100 significantly inhibited tumor growth, while AMD3100-treated PC-3 tumors had lower levels of microvessel formation and a lower immunoreactivity for the proliferation marker Ki-67 and the anti-apoptotic marker Bcl-2 compared to control tumors in vivo. The CXCR4-specific antagonist inhibits SDF-1-induced CXCR4/Akt signal transduction, and effectively suppresses tumor growth in the PC-3 xenograft model. The present study indicates that CXCR4 targeting may represent a novel strategy for the treatment of castration-resistant prostate cancer (CRPC).


Related Articles

  • Expression of the Chemokine Receptor CXCR7 in CXCR4-Expressing Human 143B Osteosarcoma Cells Enhances Lung Metastasis of Intratibial Xenografts in SCID Mice. Brennecke, Patrick; Arlt, Matthias J. E.; Muff, Roman; Campanile, Carmen; Gvozdenovic, Ana; Husmann, Knut; Holzwarth, Nathalie; Cameroni, Elisabetta; Ehrensperger, Felix; Thelen, Marcus; Born, Walter; Fuchs, Bruno // PLoS ONE;Sep2013, Vol. 8 Issue 9, p1 

    More effective treatment of metastasizing osteosarcoma with a current mean 5-year survival rate of less than 20% requires more detailed knowledge on mechanisms and key regulatory molecules of the complex metastatic process. CXCR4, the receptor of the chemokine CXCL12, has been reported to...

  • Positron Emission Tomography Imaging of Tumors Expressing the Human Chemokine Receptor CXCR4 in Mice with the Use of Cu-AMD3100. Weiss, Ido; Jacobson, Orit; Kiesewetter, Dale; Jacobus, John; Szajek, Lawrence; Chen, Xiaoyuan; Farber, Joshua M. // Molecular Imaging & Biology;Feb2012, Vol. 14 Issue 1, p106 

    Purpose: Expression of CXCR4 in cancers has been correlated with poor prognosis and increased metastasis. Quantifying CXCR4 expression non-invasively might aid in prognostication and monitoring therapy. We evaluated a radiolabeled antagonist of CXCR4, Cu-AMD3100, as a positron-emitting imaging...

  • Initial Assessment of the Role of CXC Chemokine Receptor 4 after Polytrauma. Bach, IV, Harold H.; Saini, Vikas; Baker, Todd A.; Tripathi, Abhishek; Gamelli, Richard L.; Majetschak, Matthias // Molecular Medicine;Jul2012, Vol. 18 Issue 7, p1056 

    CXC chemokine receptor (CXCR)-4 agonists have been shown to attenuate inflammation and organ injury in various disease models, including trauma/hemorrhage. The pathophysiological role of CXCR4 during the early response to tissue injury, however, remains unknown. Therefore, we investigated the...

  • Diversity and inter-connections in the CXCR4 chemokine receptor/ligand family: molecular perspectives. Pawig, Lukas; Klasen, Christina; Weber, Christian; Bernhagen, Jürgen; Noels, Heidi // Frontiers in Immunology;Aug2015, p1 

    CXCR4 and its ligand CXCL12 mediate the homing of progenitor cells in the bone marrow and their recruitment to sites of injury, as well as affect processes such as cell arrest, survival, and angiogenesis. CXCL12 was long thought to be the sole CXCR4 ligand, but more recently the atypical...

  • In vivo knockdown of CXCR4 using jetPEI/CXCR4 shRNA nanoparticles inhibits the pulmonary metastatic potential of B16-F10 melanoma cells. ANDRÉ, NAYARA DELGADO; OLIVEIRA SILVA, VIVIANE ALINE; ARIZA, CAROLINA BATISTA; EHARA WATANABE, MARIA ANGELICA; DE LUCCA, FERNANDO LUIZ // Molecular Medicine Reports;2015, Vol. 12 Issue 6, p8320 

    Metastasis is a key factor that limits survival in the majority of patients with cancer. Thus, numerous efforts have been made to elucidate the molecular mechanisms involved in this phenomenon. B16-F10 melanoma cells have been demonstrated to be highly metastatic to the lungs in mice. The aim of...

  • Signalling: Chemokine underpinnings of a tumour. Burgess, Darren J. // Nature Reviews Cancer;Apr2013, Vol. 13 Issue 4, p221 

    The article discusses the potential therapeutic value of CXCR4 chemokine for malignant peripheral nerve sheath tumours (MPNTs), referencing the study "CXCR4/CXCL12 mediate autocrine cell- cycle progression in NF1-associated malignant peripheral nerve sheath tumors," by W. Mo and colleagues.

  • CXCR1/2 Inhibition Blocks and Reverses Type 1 Diabetes in Mice. Citro, Antonio; Valle, Andrea; Cantarelli, Elisa; Mercalli, Alessia; Pellegrini, Silvia; Liberati, Daniela; Daffonchio, Luisa; Kastsiuchenka, Olga; Ruffini, Pier Adelchi; Battaglia, Manuela; Allegretti, Marcello; Piemonti, Lorenzo // Diabetes;Apr2015, Vol. 64 Issue 4, p1329 

    Chemokines and their receptors have been associated with or implicated in the pathogenesis of type 1 diabetes (T1D), but the identification of a single specific chemokine/receptor pathway that may constitute a suitable target for the development of therapeutic interventions is still lacking....

  • The CXCR4/CXCR7/CXCL12 Axis Is Involved in a Secondary but Complex Control of Neuroblastoma Metastatic Cell Homing. Mühlethaler-Mottet, Annick; Liberman, Julie; Ascenção, Kelly; Flahaut, Marjorie; Balmas Bourloud, Katia; Yan, Pu; Jauquier, Nicolas; Gross, Nicole; Joseph, Jean-Marc // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    Neuroblastoma (NB) is one of the most deadly solid tumors of the young child, for which new efficient and targeted therapies are strongly needed. The CXCR4/CXCR7/CXCL12 chemokine axis has been involved in the progression and organ-specific dissemination of various cancers. In NB, CXCR4...

  • Article Dual CXCR4 and E-Selectin Inhibitor, GMI-1359, Shows Anti-Bone Metastatic Effects and Synergizes with Docetaxel in Prostate Cancer Cell Intraosseous Growth. Festuccia, Claudio; Mancini, Andrea; Gravina, Giovanni Luca; Colapietro, Alessandro; Vetuschi, Antonella; Pompili, Simona; Ventura, Luca; Monache, Simona Delle; Iorio, Roberto; Del Fattore, Andrea; Fogler, William; Magnani, John // Cells (2073-4409);Jan2020, Vol. 9 Issue 1, Following p1 

    Metastatic castration resistant prostate cancer (mCRPC) relapses due to acquired resistance to docetaxel-based chemotherapy and remains a major threat to patient survival. In this report, we tested the effectiveness of a dual CXCR4/E-selectin antagonist, GM-I1359, in vitro and in vivo, as a...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics