Molecular regulation, membrane association and secretion of tumor cathepsin B

Upregulation, membrane association and secretion of cathepsin B have been s hown to occur in many types of tumors and to correlate positively with thei r invasive and metastatic capabilities. To further understand changes in ca thepsin B activity and localization, we have been examining its regulation at many levels including transcription and trafficking. Our studies indicat e that there may be three promoter regions in the cathepsin B gene. Of thes e, continued examination of the promoter upstream of exon 1 has indicated p ossible control by several regulatory factors including E-box and Sp-1 bind ing elements. Upregulation of cathepsin B at this level may account for som e of the secretion of cathepsin B found in tumors. We have also gathered ev idence that endo- and exocytosis of cathepsin B may be regulated by ras and ras-related proteins in addition to previously described trafficking syste ms. There is also evidence that several populations of lysosomes may exist and that trafficking to different populations may determine whether catheps in B is secreted from the tumor cell or remains intracellular. Our results indicate that membrane association and secretion of cathepsin B is not a ra ndom process in the tumor cell, but rather part of a tightly controlled sys tem.