Breast cancer cathepsins

Wolf M, Clark-Lewis I, Buii C et al (2003) Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer. Am J Pathol 162 1183-1190... 

Bl 1. Briozzo, P., Morisset, M., Capony, F., Rougeot, C., and Rochefort, H., In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells. Cancer Res. 48, 3688-3692 (1988). 

II. Isola, J., Weitz, S., Visakorpi, T., Holli, K., Shea, R., Khalbaz, N., and Kallioniemi, O.-P., Cathepsin D expression detected by immunohistochemistry has independent prognostic value in auxiliary node-negative breast cancer. J. Clin. Oncol. 11, 36-43 (1993). 

R3. Rochefort, H., Cathepsin D in breast cancer A tissue marker associated with metastasis. Eur. 

Tedone, T., Correale, M., Barbarossa, G., Casavola, V., Paradiso, A, and Reshkin, S.J., 1997, Release of the aspartyl protease cathepsin D is associated with and facilitates human breast cancer ceU invasion. FASEB J. 11 785-792... 

Harbeck N, Alt U, Berger U et al (2001) Prognostic impact of proteolytic factors (urokinase-type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy. Clin Cancer Res 7 2757-2764... 

Foekens JA, Kos J, Peters HA et al (1998) Prognostic significance of cathepsins B and L in primary human breast cancer. J Clin Oncol 16 1013-1021... 

We tested combiBUILD by using it to help design inhibitors for cathepsin D. Cathepsin D is an aspartyl protease whose structure has been solved with the inhibitor pepstatin. It is implicated in several disease processes including Alzheimer s amyloid plaque formation and breast cancer metastasis. Our goal was to design a small library of 1000 compounds of possible inhibitors to Cathepsin D. 

Cavailles, V., P. Augereau, M. Garcia and H. Rochefort. Estrogens and growth factors induce the mRNA of the 52K-pro-cathepsin-D secreted by breast cancer cells. Nucleic Acids Res. 16 1903-1919, 1988. 

INTERNET LINK Cathepsin D as a Marker for Breast Cancer... 

The CyD-peptide conjugate 79 quantitatively inhibited the endogenous cathepsin B activity of lysates of MCF-7 breast cancer cells at nanomolar concentrations identical to those determined for the isolated enzyme. Even at the concentrations required for full inhibition of extracellular and/or membrane-bound cathepsin B the... 

AA A1 A01.009 Cathepsin D Diagnosis and prognosis of breast and other cancers... 

Foekens JA, Look MP, Bolt-de Vries J. Cathepsin-D in primary breast caricer prognostic evaluation involving 2810 patients. Br J Cancer 1999 79 ... 

Several lines of evidence indicate that neoplastic cells per se are the main source of extracellular thiol proteinase activity. Recent studies (39) have shown that malignant human breast tumors maintained in organ culture secrete high levels of a cathepsin B-like enzyme into the culture medium. Moreover high levels of cathepsin B-like enzyme are present in the serum of patients with a wide variety of cancers, and these levels decrease when the cancer tissue is removed or treated with therapeutic agents (64, 65). Cathepsin B-like enzyme from cultured cells of malignant tumors (39,66) possesses enzymic properties similar to those of cathepsin B with respect to specificity, affinity, and pH optima for synthetic substrates. It hydrolyzes Bz-Arg-Arg-2-naphthylamide and is inhibited by leupeptin. However, the tumor enzyme is much more stable than cathepsin B to inactivation above pH 7. It has a molecular weight of about 33,000-35,000. The distribution of cathepsin B-like activity was determined in fractions of control and neoplastic epithelial cells from human ectocervix (66). The activity is present mainly in the mitochondrial and lysosomal fractions of normal cells but mainly in the plasma membranes and nuclei of neoplastic cells. 

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