Reference - Detail
| RRC ID | 43177 |
|---|---|
| Author | Kawakubo T, Okamoto K, Iwata J, Shin M, Okamoto Y, Yasukochi A, Nakayama KI, Kadowaki T, Tsukuba T, Yamamoto K. |
| Title | Cathepsin E prevents tumor growth and metastasis by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface. |
| Journal | Cancer Res |
| Abstract |
The aspartic proteinase cathepsin E is expressed predominantly in cells of the immune system and highly secreted by activated phagocytes, and deficiency of cathepsin E in mice results in a phenotype affecting immune responses. However, because physiologic substrates for cathepsin E have not yet been identified, the relevance of these observations to the physiologic functions of this protein remains speculative. Here, we show that cathepsin E specifically induces growth arrest and apoptosis in human prostate carcinoma tumor cell lines without affecting normal cells by catalyzing the proteolytic release of soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from the cell surface. The antitumor activity of cathepsin E was corroborated by in vivo studies with mice bearing human and mouse tumor transplants. Administration of purified cathepsin E into human tumor xenografts in nude mice dose-dependently induced apoptosis in the tumor cells to inhibit tumor growth. The growth, viability, and metastasis of mouse B16 melanoma cells were also more profound in cathepsin E-deficient mice compared with those in the syngeneic wild-type and transgenic mice overexpressing cathepsin E. Taken together, the number of apoptotic tumor cells, as well as tumor-infiltrating activated macrophages, was apparently reduced in cathepsin E-deficient mice compared with those in the other two groups, implying the positive correlation of endogenous cathepsin E levels with the extent of tumor suppression in vivo. These results thus indicate that cathepsin E plays a substantial role in host defense against tumor cells through TRAIL-dependent apoptosis and/or tumor-associated macrophage-mediated cytotoxicity. |
| Volume | 67(22) |
| Pages | 10869-78 |
| Published | 2007-11-15 |
| DOI | 10.1158/0008-5472.CAN-07-2048 |
| PII | 67/22/10869 |
| PMID | 18006832 |
| MeSH | Animals Apoptosis Carcinoma / metabolism Cathepsin E / metabolism* Cell Membrane / metabolism* Humans Immune System Male Mice Mice, Inbred C57BL Mice, Transgenic Models, Biological Neoplasm Metastasis Neoplasms / metabolism* Prostatic Neoplasms / metabolism TNF-Related Apoptosis-Inducing Ligand / metabolism* |
| IF | 9.727 |
| Times Cited | 62 |
| WOS Category | ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | B16 melanoma |