Possible role of procathepsin D in human cancer

  title={Possible role of procathepsin D in human cancer},
  author={Aruna Vashishta and Martin Fusek and V{\'a}clav Vetvicka},
  journal={Folia Microbiologica},
For the past ten years, our research has been focused on elucidating the mechanism by which procathepsin D (pCD) impacts cancer development. Various studies have shown that pCD is overexpressed and secreted by numerous cancer cell lines. After secretion, it exhibits “growth hormone-like” activity on cancerous cells but the exact mechanism of this mitogenic activity is not yet understood. The activation peptide of pCD (APpCD) (which is cleaved off upon activation of the zymogen) is responsible… Expand
Effect of procathepsin D activation peptide on gene expression of breast cancer cells.
Several differentially expressed genes involved in signal transduction, regulation of cell cycle, apoptosis, tumor invasion and metastasis were identified using microarray technology and were confirmed in breast cancer cell lines by reverse-transcriptase PCR (RT-PCR). Expand
Cathepsin D--many functions of one aspartic protease.
The possible functions of cathepsin D and its various forms in cells and organisms during physiological and pathological conditions are reviewed. Expand
Schistosoma Mansonii aspartic protease expression and refolding trials
Preliminary evidence suggests that an activated form of one of the two proteases (SmCD2) may be obtained by introducing a solubilizing maltosebinding tag on the N-terminal end resulting in soluble expression of the enzyme, and raised the prospect of developing an in vitro screening tool to identify potential lead compounds for new drug development. Expand
Cathepsins: Getting in Shape for Lysosomal Proteolysis
It is crucial to understand the molecular basis of cathepsin biosynthesis and intracellular transport as well as the mechanisms leading to activation of their precursors in a cellular context to prevent tissue damage due to unwanted proteolysis. Expand


Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors
Different mechanisms by which pCD could promote development and spread of cancer cells are discussed, which seem to involve interaction of the activation peptide with as yet unidentified receptor. Expand
Mitogenic function of human procathepsin D: the role of the propeptide.
The results indicate that the mitogenic function involves the propeptide of cathepsin D, which appears to be recognized by a surface receptor. Expand
Effect of procathepsin D and its activation peptide on prostate cancer cells.
The first experimental data showing the direct effects of procathepsin D on prostate cancer cells are shown, and the level of proliferation of these cell lines depending on the presence of either procat hepsin or activation peptide in the medium is tested. Expand
Anti‐human procathepsin D activation peptide antibodies inhibit breast cancer development
It is hypothesized that the interaction of procathepsin D activation peptide with an unknown surface receptor is mediated by a sequence 36–44 plus close vicinity and it is proposed that this interaction leads in certain types of tumor derived cell lines to proliferation and higher motility. Expand
Analysis of the interaction of procathepsin D activation peptide with breast cancer cells
In vivo experiments indicate that treatment with anti‐procathepsin D antibodies can reverse the growth of human breast tumors in athymic nude mice and that the binding activity can be localized in position 27–44 of the activation peptide of procathePSin D. Expand
Modulation of proliferation and chemosensitivity by procathepsin D and its peptides in ovarian cancer.
There are several unique forms of cathepsin D expressed and accumulated by ovarian tumors and these forms are detectable in the sera of those with ovarian cancer, which can increase the proliferation of these tumor cells, while decreasing their sensitivity to chemotherapeutic agents. Expand
Cathepsin D in the malignant progression of neoplastic diseases (review).
Findings warrant extensive experimental and clinical studies to better assess the pathophysiological role of this acid proteinase in the spread of neoplastic diseases and suggest new and more selective therapeutic approaches to the treatment of human neoplasms. Expand
Cathepsin D expression levels in nongynecological solid tumors: Clinical and therapeutic implications
Evidence emerging from these studies indicates that this proteinase seems to facilitate early phases of tumor progression such as cell proliferation and local dissemination, which supports the concept that cathepsin D may be a useful marker for identifying patients with highly malignant tumor phenotypes who may need more aggressive clinical treatment. Expand
Biological and clinical significance of cathepsin D in breast cancer.
In nude mice, transfection of cathepsin D cDNA into tumor cells increases their metastatic potential, suggesting that overexpression of this protease may be one of the factors responsible for metastasis in human breast cancer. Expand
Human procathepsin D: three-dimensional model and isolation.
The isolation of human procathepsin D from medium of human breast cancer cell line ZR-75-1 potentiated with estrogen involved both immunoaffinity chromatography and ion-exchange chromatography. Expand