Affiliation: University of Louisville,Department of Pathology, 511 S. Floyd, Louisville, KY, USA.
Procathepsin D (pCD) is overexpressed and secreted by cells of various tumor types including breast and lung carcinomas, affecting multiple features of tumor cells including proliferation, invasion, metastasis and apoptosis. As more and more attention has been focused on potential use of pCD in clinical practice, we devoted this paper to summarize the three major potentials of pCD — tumor marker, potential drug and screening agent. Despite more than 20 years of studies and numerous reports of the association between pCD level and tumor size, tumor grade, tumor aggressiveness, and incidence of metastasis, pCD is still not used as a marker of cancer development. This is due to problems in distinguishing between pCD expressed by cancer derived cells and normal tissue cells and in the exact measuring of its different molecular forms (pCD, single chain cathepsin D (CD) and two chain CD) in tumor tissue. Numerous studies demonstrated that pCD secreted from cancer cells affects multiple stages of tumor progression. Subsequent data showing that inhibition of pCD secretion from cancer cells can inhibit cancer cell growth in vitro and in vivo suggested the possibility of using pCD suppression in clinical practice. A third possibility of using pCD in clinical practice is represented by the use of anti-pCD autoantibodies in screening cancer patients or in correlation with the level of these antibodies with the progress of cancer disease. Despite the fact that preliminary findings suggested such correlation, more detailed studies revealed significant setbacks.