Significance of the expression of the growth factor pleiotrophin in pancreatic cancer patients.

PURPOSE Recently, we found that pleiotrophin (PTN) acts as a rate-limiting autocrine growth factor in pancreatic cancer cells. The aim of this study was to determine the expression pattern of PTN in pancreatic cancer and to analyze the clinical significance of PTN in pancreatic cancer patients. EXPERIMENTAL DESIGN We compared PTN expression in malignant (n = 24), inflammatory (n = 13), and normal (n = 14) pancreatic tissues using immunohistochemistry and in situ hybridization and determined PTN serum levels in pancreatic cancer patients (n = 77), in patients suffering from chronic pancreatitis (n = 21), and in healthy volunteers (n = 28). Two-year survival rates were determined for pancreatic cancer patients in relation to serum levels of PTN. RESULTS The frequency of PTN expression increased from normal tissue (7%) to inflammatory (34%) and pancreatic cancer tissues (67%; P < 0.05). Compared with a healthy control group, we found elevated PTN serum levels in 30% of patients with chronic pancreatitis (mean, 143 +/- 55 pg/ml) and in 53% of pancreatic cancer patients (mean, 200 +/- 29 pg/ml; P < 0.05). Elevated serum levels of PTN dropped in patients after successful tumor resection but were unaffected when only palliative surgery was performed (P < 0.0001). High preoperative serum PTN levels correlated with a worse 2-year survival (P < 0.05). CONCLUSIONS This study supports the clinical significance of PTN for the malignant progression of pancreatic cancer.

[1]  H. Juhl,et al.  Relationship between serum concentrations of the growth factor pleiotrophin and pleiotrophin-positive tumors. , 1998, Journal of the National Cancer Institute.

[2]  C. Boland,et al.  American Gastroenterological Association. Our new president--Jon I. Isenberg, M.D. , 2001, Gastroenterology.

[3]  A. Wellstein,et al.  Melanoma angiogenesis and metastasis modulated by ribozyme targeting of the secreted growth factor pleiotrophin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Wellstein,et al.  Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an endogenous retrovirus. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Tempero,et al.  AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. American Gastroenterological Association. , 1999, Gastroenterology.

[6]  S. Donnini,et al.  An angiogenic role for the neurokines midkine and pleiotrophin in tumorigenesis. , 1997, Cancer research.

[7]  T. Deuel,et al.  Pleiotrophin transforms NIH 3T3 cells and induces tumors in nude mice. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Wellstein,et al.  Pleiotrophin stimulates fibroblasts and endothelial and epithelial cells and is expressed in human cancer. , 1992, The Journal of biological chemistry.

[9]  H. Juhl,et al.  Pleiotrophin can be rate-limiting for pancreatic cancer cell growth. , 2000, Cancer research.

[10]  A. Abioye,et al.  Pancreatic carcinoma. , 2020, Journal of the National Medical Association.

[11]  A. Wellstein,et al.  Influence of the human endogenous retrovirus-like element HERV-E.PTN on the expression of growth factor pleiotrophin: a critical role of a retroviral Sp1-binding site , 2000, Oncogene.

[12]  N. Wright,et al.  Growth factors and growth factor receptors. , 1993, British journal of hospital medicine.

[13]  A. Wellstein,et al.  Ribozyme-targeting elucidates a direct role of pleiotrophin in tumor growth. , 1994, The Journal of biological chemistry.