Somatostatin effects on the proteome of the LNCaP cell-line.

Some clinical results indicate that somatostatin (sms) might be useful in the treatment of advanced prostate cancer (HRPC). Because of its transient in vivo half-life only more stable derivatives of sms are of interest in this context. Recent studies have shown that natural sms can be conjugated to a carbohydrate (smsdx) with preservation of sms-like effects on the prostatic tumor cell proteome. The present study identifies some of the affected proteins in an effort to elucidate pathways and proteins that might be of importance for the potential usefulness of sms treatment in HRPC. After incubating the LNCaP cell-line with sms14/smsdx, comparative proteomics was used for analysing and identifying affected proteins. Protein expression patterns were analysed with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Catalytic mitochondrial and mitochondrial-associated proteins were significantly affected (fold change approximately 2 or higher) and they were in general up-regulated. Apoptosis-related proteins were both up-regulated (VDAC1, VDAC2) and down-regulated (PRDX2, TCTP). The fold change was >2 for PRDX2 and <2 for the others. There was a strong agreement between sms and smsdx on the up- and down-regulation of proteins. Sms/smsdx triggered up-regulation of catalytic mitochondrial proteins and seemed to affect apoptosis-related proteins. This could indicate important pathways on which smsdx might be able to curb the progression of HRPC. The results encourage a pending clinical phase II study.

[1]  A. Sciarra,et al.  New perspective in the management of neuroendocrine differentiation in prostate adenocarcinoma , 2006, International journal of clinical practice.

[2]  S. Nilsson,et al.  Proteomic Analysis of a Human Prostate Cancer Cell Line after Incubation with a Novel Somatostatin14 Derivative. , 2005, Cancer genomics & proteomics.

[3]  E. Baumgart-Vogt,et al.  Peroxiredoxins, oxidative stress, and cell proliferation. , 2005, Antioxidants & redox signaling.

[4]  R. Kim,et al.  Recent advances in understanding the cell death pathways activated by anticancer therapy , 2005, Cancer.

[5]  T. Mak,et al.  DJ-1, a novel regulator of the tumor suppressor PTEN. , 2005, Cancer cell.

[6]  H. Joensuu,et al.  Phase I Trial on sms‐D70 Somatostatin Analogue in Advanced Prostate and Renal Cell Cancer , 2004, Annals of the New York Academy of Sciences.

[7]  D. Moras,et al.  Translationally controlled tumor protein is a target of tumor reversion. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  W. Arap,et al.  Cell surface expression of the stress response chaperone GRP78 enables tumor targeting by circulating ligands. , 2004, Cancer cell.

[9]  Y. Hod.  Differential control of apoptosis by DJ‐1 in prostate benign and cancer cells , 2004, Journal of cellular biochemistry.

[10]  P. Tosi,et al.  Translationally controlled tumor protein (TCTP) in the human prostate and prostate cancer cells: Expression, distribution, and calcium binding activity , 2004, The Prostate.

[11]  E. Woltering,et al.  Somatostatin analogs: angiogenesis inhibitors with novel mechanisms of action , 2004, Investigational New Drugs.

[12]  M. Mirande,et al.  Translationally controlled tumor protein acts as a guanine nucleotide dissociation inhibitor on the translation elongation factor eEF1A , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Y. Hod,et al.  Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: identification of RS/DJ-1 and RhoGDIalpha. , 2003, Cancer research.

[14]  Alfons Lawen,et al.  Apoptosis—an introduction , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[15]  Eric Vivier,et al.  Critical role of Src and SHP-2 in sst2 somatostatin receptor-mediated activation of SHP-1 and inhibition of cell proliferation. , 2003, Molecular biology of the cell.

[16]  E. Solary,et al.  Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. , 2003, Biochemical and biophysical research communications.

[17]  Kim-Anh Do,et al.  Fingerprinting the circulating repertoire of antibodies from cancer patients , 2003, Nature Biotechnology.

[18]  Z. A. Wood,et al.  Structure, mechanism and regulation of peroxiredoxins. , 2003, Trends in biochemical sciences.

[19]  S. Pizzo,et al.  The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction. , 2002, The Journal of biological chemistry.

[20]  E. Small,et al.  Hormone-Refractory prostate cancer , 2002, Current treatment options in oncology.

[21]  S. Nilsson,et al.  A novel somatostatin conjugate with a high affinity to all five somatostatin receptor subtypes , 2002, Cancer.

[22]  Carl Nathan,et al.  Nonredundant Antioxidant Defense by Multiple Two-Cysteine Peroxiredoxins in Human Prostate Cancer Cells , 2002, Molecular medicine.

[23]  K. Fujise,et al.  Characterization of Fortilin, a Novel Antiapoptotic Protein* , 2001, The Journal of Biological Chemistry.

[24]  G. Atweh,et al.  Stathmin Inhibition Enhances Okadaic Acid-induced Mitotic Arrest , 2001, The Journal of Biological Chemistry.

[25]  S. Nilsson,et al.  Biodistribution, blood half-life, and receptor binding of a somatostatin-dextran conjugate , 2001, Medical oncology.

[26]  Ming-Shyue Lee,et al.  DIFFERENTIAL RESPONSIVENESS OF PROSTATIC ACID PHOSPHATASE AND PROSTATE‐SPECIFIC ANTIGEN mRNA TO ANDROGEN IN PROSTATE CANCER CELLS , 2000, Cell biology international.

[27]  D. Schadendorf,et al.  Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two‐dimensional electrophoresis , 2000, Electrophoresis.

[28]  G. Kroemer,et al.  Mitochondrion as a novel target of anticancer chemotherapy. , 2000, Journal of the National Cancer Institute.

[29]  Guido Kroemer,et al.  Mitochondrial control of cell death , 2000, Nature Medicine.

[30]  Masashi Narita,et al.  Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC , 1999, Nature.

[31]  A. Schally,et al.  Inhibition of PC-3 human androgen-independent prostate cancer and its metastases by cytotoxic somatostatin analogue AN-238. , 1999, Cancer research.

[32]  F. Gago,et al.  Heat shock protein expression and drug resistance in breast cancer patients treated with induction chemotherapy , 1998, International journal of cancer.

[33]  C. B. Srikant,et al.  Induction of wild‐type p53, Bax, and acidic endonuclease during somatostatin‐signaled apoptosis in MCF‐7 human breast cancer cells , 1998, International journal of cancer.

[34]  L. Oberley,et al.  Expression of antioxidant enzymes in human prostatic adenocarcinoma , 1997, The Prostate.

[35]  S. Horwitz,et al.  The Microtubule-destabilizing Activity of Metablastin (p19) Is Controlled by Phosphorylation* , 1997, The Journal of Biological Chemistry.

[36]  H. Gradin,et al.  Oncoprotein 18 is a phosphorylation‐responsive regulator of microtubule dynamics. , 1996, The EMBO journal.

[37]  H. Grönberg,et al.  Differentiation‐stage specific expression of oncoprotein 18 in human and rat prostatic adenocarcinoma , 1995, The Prostate.

[38]  R. Bianchi,et al.  Direct inhibitory effect of somatostatin on the growth of the human prostatic cancer cell line LNCaP: possible mechanism of action. , 1993, The Journal of clinical endocrinology and metabolism.

[39]  G. Auer,et al.  Nonenzymatic extraction of cells from clinical tumor material for analysis of gene expression by two‐dimensional polyacrylamide gel electrophoresis , 1993, Electrophoresis.

[40]  M. Lin,et al.  Regulation of prostatic acid phosphatase expression and secretion by androgen in LNCaP human prostate carcinoma cells. , 1993, Archives of biochemistry and biophysics.

[41]  M. Blankenstein,et al.  Effect of culture conditions on androgen sensitivity of the human prostatic cancer cell line LNCaP , 1993, The Prostate.

[42]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[43]  S. Arya,et al.  The LNCaP cell line--a new model for studies on human prostatic carcinoma. , 1980, Progress in clinical and biological research.