Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells

被引：185

作者：

Nomura, Toshiyuki ^{[1
]}

Katunuma, Nobuhiko

机构：

[1] Takeda Pharmaceut Co Ltd, Pharmacol Res Labs 1, Osaka, Japan

来源：

JOURNAL OF MEDICAL INVESTIGATION | 2005年 / 52卷 / 1-2期

关键词：

cancer; cathepsins; inhibitors; invasion; metastasis;

D O I：

10.2152/jmi.52.1

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Tumor cell invasion and metastasis are associated with the proteolytic activity of various types of proteinases. Among them, cathepsins, which are lysosomal proteinases, have receivedmore attention recently. Since elevated expressions of cathepsins anddiminished levels of their inhibitors have been observed in several human cancers, including breast, gastric andprostate cancer, especially in aggressive cancer cells, cathepsinshave been suggested to be biological markers of malignant tumors and have proved useful for prognosis of the disease. Furthermore, cathepsins have various roles in cancer progression. CathepsinDhas a mitogenic activity independent of its proteolytic activity and it attenuates the anti- tumor immune response of decaying chemokines to inhibit the function of dendritic cells. Cathepsins B and L have been shown to play an important role in matrix degradation and cell invasion. The administration of their inhibitors prevents the invasion and metastasis of cancer cells. These results indicate that cancer cells orchestrate various cathepsins to progressmalignant diseases. Cathepsins may be a potential target for cancer therapy.

引用

页码：1 / 9

页数：9

共 64 条

[1] Liotta L.A., Rao C.N., Wewer U.M., Biochemical interactions of tumor cells with the basement membrane, Annu Rev Biochem, 55, pp. 1037-1035, (1986)
[2] Woodhouse E.C., Chuaqui R.F., Liotta L.A., General mechanisms of metastasis, Cancer, 80, pp. 1529-1537, (1997)
[3] Kos J., Lah T.T., Cysteine proteinases and their endogenous inhibitors: Target proteins for prognosis, diagnosis and therapy in cancer, Oncol Rep, 5, pp. 1349-1346, (1998)
[4] Foekens J.A., Look M.P., Bolt-De Vries J., Meijer-Van Gelder M.E., Van Putten W.L., Klijn J.G., Cathepsin-D in primary breast cancer: Prognostic evaluation involving 2810 patients, Br J Cancer, 79, pp. 300-307, (1999)
[5] Lah T.T., Cercek M., Blejec A., Kos J., Gorodetsky E., Somers R., Daskal I., Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: Comparison with cathepsin D, cathepsin L, and other clinical indicators, Clin Cancer Res, 6, pp. 578-584, (2000)
[6] Joyce J.A., Baruch A., Chehade K., Meyer-Morse N., Giraudo E., Tsai F.Y., Greenbaum D.C., Hager J.H., Bogyo M., Hanahan D., Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis, Cancer Cell, 5, pp. 443-453, (2004)
[7] Gabel C.A., Goldberg D.E., Kornfeld S., Identification and characterization of cells deficient in the mannose 6-phosphate receptor: Evidence for an alternate pathway for lysosomal enzyme targeting, Proc Natl Acad Sci USA, 80, pp. 775-779, (1983)
[8] Rochefort H., Cathepsin D in breast cancer: A tissue marker associated with metastasis, Eur J Cancer, 28 A, pp. 1780-1783, (1992)
[9] Ferrandina G., Scambia G., Bardelli F., Benedetti Panici P., Mancuso S., Messori A., Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: A meta-analysis, Br J Cancer, 76, pp. 661-666, (1997)
[10] Cherry J.P., Mordente J.A., Chapman J.R., Choudhury M.S., Tazaki H., Mallouh C., Konno S., Analysis of cathepsin D forms and their clinical implications in human prostate cancer, J Urol, 160, 6 PART 1, pp. 2223-2228, (1998)

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