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

Tumor cell invasion and metastasis are associated with the proteolytic activity of various types of proteinases. Among them, cathepsins, which are lysosomal proteinases, have received more attention recently. Since elevated expressions of cathepsins and diminished levels of their inhibitors have been observed in several human cancers, including breast, gastric and prostate cancer, especially in aggressive cancer cells, cathepsins have 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. Cathepsin D has 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 progress malignant diseases. Cathepsins may be a potential target for cancer therapy.

[1]  K. Bakunts,et al.  Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: distribution and functional activity. , 2004, American journal of physiology. Cell physiology.

[2]  D. Hanahan,et al.  Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. , 2004, Cancer cell.

[3]  H. Band,et al.  Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells , 2004, Oncogene.

[4]  P. Allavena,et al.  Chemokines and Dendritic Cell Traffic , 2000, Journal of Clinical Immunology.

[5]  V. Vetvicka,et al.  Anti‐human procathepsin D activation peptide antibodies inhibit breast cancer development , 1999, Breast Cancer Research and Treatment.

[6]  I. Silver,et al.  Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism , 1997, Clinical & Experimental Metastasis.

[7]  L. Mazzucchelli,et al.  Cathepsin D Specifically Cleaves the Chemokines Macrophage Inflammatory Protein-1α, Macrophage Inflammatory Protein-1β, and SLC That Are Expressed in Human Breast Cancer , 2003 .

[8]  Bonnie F. Sloane,et al.  Invasiveness of Transformed Human Breast Epithelial Cell Lines Is Related to Cathepsin B and Inhibited by Cysteine Proteinase Inhibitors , 2003, Biological chemistry.

[9]  R. Colella,et al.  Decreased activity of cathepsins L+B and decreased invasive ability of PC3 prostate cancer cells , 2003, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[10]  L. Mazzucchelli,et al.  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. , 2003, The American journal of pathology.

[11]  T. Lah,et al.  Expression of cysteine peptidase cathepsin L and its inhibitors stefins A and B in relation to tumorigenicity of breast cancer cell lines. , 2002, Cancer letters.

[12]  E. Goodwyn,et al.  Increased cell density decreases cysteine proteinase inhibitor activity and increases invasive ability of two prostate tumor cell lines. , 2002, Cancer letters.

[13]  G. Berchem,et al.  Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis , 2002, Oncogene.

[14]  Marcel Garcia,et al.  Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells , 2002, Oncogene.

[15]  N. Ishimaru,et al.  Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. , 2002, The Journal of clinical investigation.

[16]  D. Gleason,et al.  Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma , 2002, Cancer.

[17]  B. Fingleton,et al.  Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations , 2002, Science.

[18]  A. Blejec,et al.  Comparison of potential biological markers cathepsin B, cathepsin L, stefin A and stefin B with urokinase and plasminogen activator inhibitor-1 and clinicopathological data of breast carcinoma patients. , 2002, Cancer detection and prevention.

[19]  A. Zlotnik,et al.  Chemokines: agents for the immunotherapy of cancer? , 2002, Nature Reviews Immunology.

[20]  Christophe Caux,et al.  Tumour escape from immune surveillance through dendritic cell inactivation. , 2002, Seminars in cancer biology.

[21]  H. Tsuge,et al.  Structure-based design of specific cathepsin inhibitors and their application to protection of bone metastases of cancer cells. , 2002, Archives of biochemistry and biophysics.

[22]  V. Laurent-Matha,et al.  A mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells , 2001, Oncogene.

[23]  H. Saji,et al.  Significant correlation of monocyte chemoattractant protein‐1 expression with neovascularization and progression of breast carcinoma , 2001, Cancer.

[24]  G. Fuller,et al.  Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells , 2001, Oncogene.

[25]  A. Szpaderska,et al.  An intracellular form of cathepsin B contributes to invasiveness in cancer. , 2001, Cancer research.

[26]  J. Manivel,et al.  A potential role for interleukin-8 in the metastatic phenotype of breast carcinoma cells. , 2001, The American journal of pathology.

[27]  Bonnie F. Sloane,et al.  Invasion of ras-Transformed Breast Epithelial Cells Depends on the Proteolytic Activity of Cysteine and Aspartic Proteinases , 2001 .

[28]  Y. Seyama,et al.  Overexpression of vacuolar ATPase 16-kDa subunit in 10T1/2 fibroblasts enhances invasion with concomitant induction of matrix metalloproteinase-2. , 2000, Biochemical and biophysical research communications.

[29]  Y. Kawakami,et al.  Immunostained cathepsins B and L correlate with depth of invasion and different metastatic pathways in early stage gastric carcinoma , 2000, Cancer.

[30]  H. Saji,et al.  Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[31]  H. Moch,et al.  Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. , 2000, Human pathology.

[32]  E. Vuorio,et al.  Antisense RNA inhibition of cathepsin L expression reduces tumorigenicity of malignant cells. , 2000, European journal of cancer.

[33]  K. Pienta,et al.  Rapid ("warm") autopsy study for procurement of metastatic prostate cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[34]  A. Blejec,et al.  Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: comparison with cathepsin D, cathepsin L, and other clinical indicators. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[35]  A. Ben-Baruch,et al.  Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. , 1999, Cancer research.

[36]  D. Turk,et al.  Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo , 1999, FEBS letters.

[37]  J. Foekens,et al.  Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients , 1999, British Journal of Cancer.

[38]  S. Loening,et al.  Cathepsins B, H, L and cysteine protease inhibitors in malignant prostate cell lines, primary cultured prostatic cells and prostatic tissue. , 1999, European journal of cancer.

[39]  H. Tazaki,et al.  Analysis of cathepsin D forms and their clinical implications in human prostate cancer. , 1998, The Journal of urology.

[40]  Y. Fujisawa,et al.  Synthesis of peptide aldehyde derivatives as selective inhibitors of human cathepsin L and their inhibitory effect on bone resorption. , 1998, Journal of medicinal chemistry.

[41]  Christoph Schaniel,et al.  Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation , 1998, European journal of immunology.

[42]  H. Höfler,et al.  Identification of low-risk node-negative breast cancer patients by tumor biological factors PAI-1 and cathepsin L. , 1998, Anticancer research.

[43]  Gerhard Christofori,et al.  A causal role for E-cadherin in the transition from adenoma to carcinoma , 1998, Nature.

[44]  J. Foekens,et al.  Prognostic significance of cathepsins B and L in primary human breast cancer. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  L. Liotta,et al.  General mechanisms of metastasis , 1997, Cancer.

[46]  G. Scambia,et al.  A META-ANALYSIS , 2005 .

[47]  D. Rich,et al.  Mechanistic studies on the inactivation of papain by epoxysuccinyl inhibitors. , 1996, Journal of medicinal chemistry.

[48]  M. Schwartz.  Tissue cathepsins as tumor markers. , 1995, Clinica chimica acta; international journal of clinical chemistry.

[49]  N. Katunuma,et al.  Structure, properties, mechanisms, and assays of cysteine protease inhibitors: cystatins and E-64 derivatives. , 1995, Methods in enzymology.

[50]  V. Vetvicka,et al.  Mitogenic function of human procathepsin D: the role of the propeptide. , 1994, The Biochemical journal.

[51]  H. Rochefort,et al.  Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[52]  A. Barrett,et al.  CA074 methyl ester: a proinhibitor for intracellular cathepsin B. , 1992, Archives of biochemistry and biophysics.

[53]  H. Rochefort,et al.  Cathepsin D in breast cancer: a tissue marker associated with metastasis. , 1992, European journal of cancer.

[54]  J. Griffiths.  Are cancer cells acidic? , 1991, British Journal of Cancer.

[55]  M. Murata,et al.  Novel epoxysuccinyl peptides Selective inhibitors of cathepsin B, in vitro , 1991, FEBS letters.

[56]  N. Katunuma,et al.  Novel epoxysuccinyl peptides A selective inhibitor of cathepsin B, in vivo , 1991, FEBS letters.

[57]  D. Steiner,et al.  Expression of five cathepsins in murine melanomas of varying metastatic potential and normal tissues. , 1989, Cancer research.

[58]  T. Maudelonde,et al.  Overexpression and hormonal regulation of pro-cathepsin D in mammary and endometrial cancer. , 1989, Journal of steroid biochemistry.

[59]  B. Turyna,et al.  [Cysteine proteinases and their endogenous inhibitors]. , 1988, Postepy biochemii.

[60]  J. Wright,et al.  Cysteine proteinase cathepsin L expression correlates closely with the metastatic potential of H-ras-transformed murine fibroblasts. , 1987, Oncogene.

[61]  Bonnie F. Sloane,et al.  Plasma membrane-associated cysteine proteinases in human and animal tumors. , 1987, Experimental cell biology.

[62]  L. Liotta,et al.  Biochemical interactions of tumor cells with the basement membrane. , 1986, Annual review of biochemistry.

[63]  D. Goldberg,et al.  Identification and characterization of cells deficient in the mannose 6-phosphate receptor: evidence for an alternate pathway for lysosomal enzyme targeting. , 1983, Proceedings of the National Academy of Sciences of the United States of America.