A glycolytic mechanism regulating an angiogenic switch in prostate cancer.

The generation of an "angiogenic switch" is essential for tumor growth, yet its regulation is poorly understood. In this investigation, we explored the linkage between metastasis and angiogenesis through CXCL12/CXCR4 signaling. We found that CXCR4 regulates the expression and secretion of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 reduced the secretion of vascular endothelial growth factor and interleukin-8 and increased the generation of angiostatin. At metastatic sites, however, high levels of CXCL12 signaling through CXCR4 reduced PGK1 expression, releasing the angiogenic response for metastastic growth. These data suggest that PGK1 is a critical downstream target of the chemokine axis and an important regulator of an "angiogenic switch" that is essential for tumor and metastatic growth.

[1]  R. Shah,et al.  The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis , 2006, BMC Cancer.

[2]  H. Kung,et al.  Interleukin-8 confers androgen-independent growth and migration of LNCaP: differential effects of tyrosine kinases Src and FAK , 2004, Oncogene.

[3]  Y. Oda,et al.  The accumulation of angiostatin-like fragments in human prostate carcinoma. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[4]  Ying Liang,et al.  Overexpression and elevated serum levels of phosphoglycerate kinase 1 in pancreatic ductal adenocarcinoma , 2006, Proteomics.

[5]  Hong Wang,et al.  Protein profiles associated with survival in lung adenocarcinoma , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S Paget,et al.  THE DISTRIBUTION OF SECONDARY GROWTHS IN CANCER OF THE BREAST. , 1889 .

[7]  T. Ratliff.  CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells. , 2005, The Journal of urology.

[8]  O. Warburg.  [Origin of cancer cells]. , 1956, Oncologia.

[9]  E. Latulippe,et al.  Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. , 2002, Cancer research.

[10]  Daohai Zhang,et al.  Proteomic Study Reveals That Proteins Involved in Metabolic and Detoxification Pathways Are Highly Expressed in HER-2/neu-positive Breast Cancer* , 2005, Molecular & Cellular Proteomics.

[11]  Evan T Keller,et al.  Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. , 2002, Cancer research.

[12]  T. Giordano,et al.  Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. , 2005, Cancer cell.

[13]  H. Moch,et al.  Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHL , 2003, Nature.

[14]  K. Pienta,et al.  Expression of CXCR4 and CXCL12 (SDF‐1) in human prostate cancers (PCa) in vivo , 2003, Journal of cellular biochemistry.

[15]  K. Pienta,et al.  Bone turnover mediates preferential localization of prostate cancer in the skeleton. , 2005, Endocrinology.

[16]  P. Hogg,et al.  Secretion of phosphoglycerate kinase from tumour cells is controlled by oxygen-sensing hydroxylases. , 2004, Biochimica et biophysica acta.

[17]  David J Mooney,et al.  Engineering and Characterization of Functional Human Microvessels in Immunodeficient Mice , 2001, Laboratory Investigation.

[18]  J. Krieger,et al.  Short tandem repeat polymorphism linkage to the androgen receptor gene in prostate carcinoma , 2001, Cancer.

[19]  Kwan Tat Steeve,et al.  IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. , 2004 .

[20]  P. Hogg,et al.  Phosphoglycerate kinase acts in tumour angiogenesis as a disulphide reductase , 2000, Nature.

[21]  Jian Zhang,et al.  Vascular endothelial growth factor contributes to prostate cancer-mediated osteoblastic activity. , 2005, Cancer research.

[22]  Abraham Schneider,et al.  Skeletal Localization and Neutralization of the SDF‐1(CXCL12)/CXCR4 Axis Blocks Prostate Cancer Metastasis and Growth in Osseous Sites In Vivo , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  Jianhua Wang,et al.  Diverse signaling pathways through the SDF-1/CXCR4 chemokine axis in prostate cancer cell lines leads to altered patterns of cytokine secretion and angiogenesis. , 2005, Cellular signalling.

[24]  P. Clézardin,et al.  Angiostatin Inhibits Bone Metastasis Formation in Nude Mice through a Direct Anti-osteoclastic Activity* , 2003, Journal of Biological Chemistry.

[25]  M. Socinski,et al.  Seeking a home for a PET, part 2: Defining the appropriate place for positron emission tomography imaging in the staging of patients with suspected lung cancer. , 2004, Chest.

[26]  K. Pienta,et al.  Expression and activation of αvβ3 integrins by SDF‐1/CXC12 increases the aggressiveness of prostate cancer cells , 2007 .

[27]  T. Cloughesy,et al.  Upregulation of tissue inhibitor of metalloproteinases (TIMP)-2 promotes matrix metalloproteinase (MMP)-2 activation and cell invasion in a human glioblastoma cell line , 2004, Laboratory Investigation.

[28]  D. Longo,et al.  Linking β-Catenin to Androgen-signaling Pathway* , 2002, The Journal of Biological Chemistry.

[29]  K. Pienta,et al.  Preferential adhesion of prostate cancer cells to a human bone marrow endothelial cell line. , 1998, Journal of the National Cancer Institute.