Pleiotrophin Can Be Rate-limiting for Pancreatic Cancer Cell Growth
2000
Pancreaticcancer is one of the most aggressive malignant tumors, with an overall
survival rate of 2%. The identification of growth factors that
contribute to the malignant phenotype can help to identify new targets
for therapy. In this study, we analyzed the growth factor pleiotrophin
(PTN) that was originally described as a developmentally regulated
cytokine during early embryogenesis. More recently, PTN was found to be
overexpressed in a variety of neuroectodermal tumors and described as
an essential angiogenic growth factor in choriocarcinoma and melanoma,
promoting metastatic growth. Recently, we discovered high expression
levels of PTN in patients with gastrointestinal malignancies,
particularly in those patients with pancreatic cancer. However, it is
not known whether PTN is a contributor to the growth of pancreatic
cancer or is only a bystander. We used ribozymes to deplete PTN mRNA
from Colo357 pancreatic cancer cells and studied the resulting
phenotype. The reduction of PTN resulted in a decrease in the
proliferation rate, soft agar colony formation, and tumor growth in
animals. Supplementation of cells with PTN partially reversed the
ribozyme effect. The autocrine function of PTN was confirmed by using
PTN-binding antibodies that inhibited the proliferation rate by 50% in
Colo357 cells but also in a different pancreatic cancer cell line,
Panc89. Our study identifies PTN as a new and essential growth factor
for pancreatic cancer. Due to the restricted expression pattern of PTN
in adults, PTN is suggested as a target for pancreatic cancer
therapy.
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