Ribozyme Targeting of the Growth Factor Pleiotrophin

The significance of blood vessel formation (angiogenesis) for the growth of solid tumors and ultimately their metastatic spread has gained wide acceptance. The close relationship between tumor angiogenesis and metastasis has been demonstrated in a series of correlative clinical studies published in the past five years after an initial report by Weidner et al. in 1991 ([1 ], which is reviewed in ref . 2 ). In our experiments, we studied the significance of pleiotrophin (PTN; Genbank accession #M57399) for melanoma angiogenesis and metastasis. PTN is a secreted polypeptide growth factor (3 ) that is expressed in a variety of established tumor cell lines and primary human tumor specimens (4 ), is a mitogen for fibroblasts (3 ), epithelial cells derived from bovine lens (5 ) or human adrenal carcinoma (4 ,6 ), and for endothelial cells (4 ,5 ). Among several tumor types expressing PTN, melanoma seemed most suitable to study the significance of an individual angiogenic factor for tumor metastasis because these tumors grow rapidly and are fatal due to their early metastatic spread in the body. Furthermore, we had observed that a number of melanoma cell lines but not melanocytes expressed this gene product (4 ).