11 Alterations in Processing and Trafficking of Cathepsin B during Malignant Progression

Sloane, Bonnie F.; Sameni, Mansoureh; Cao, Lequn; Berquin, Isabelle M.; Rozhin, Jurij; Ziegler, Grace; Moin, Kamiar; Day, Nancy A.

doi:10.1159/000423531

Cited by 18 publications

(36 citation statements)

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“…Several studies have shown involvement of mature CB in the degradation of extracellular matrix in solid organ tumors (such as human breast and colon tumors, gliomas, and murine melanoma; Buck et al, 1992;Rozhin et al, 1994;Sloane et al, 1994a,b;Reddy et al, 1995;Elliot and Sloane, 1996). Both CB and cathepsin L have been shown to be active against extracellular matrix proteins at physiological pH (Buck et al, 1992;Sloane et al, 1994b;Reddy et al, 1995). Thus, our localization study is consistent with biochemical studies showing the involvement of CB in the degradation of extracellular matrix proteins.…”

Section: Discussionsupporting

confidence: 90%

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

et al. 1998

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Cathepsin B (CB) is involved in invasion and metastasis of a variety of solid organ tumors, including human prostate cancer. The tertiary structures of the proenzyme and mature forms of CB are related closely, as revealed by crystallographic studies. However, the cellular distributions of the CB forms have not been defined in human prostate and its tumors. Our objective was to investigate the distribution and codistribution of CB and procathepsin B (proCB) in human prostate tumors. Human prostate tissue samples that were obtained from 21 prostatectomy and/or cystectomy patients were collected immediately after surgery and processed for this study. We used a rabbit antihuman liver CB immunoglobulin G (IgG) that recognizes both mature CB and proCB and a mouse antipropeptide monoclonal antibody IgG that recognizes only proCB. Fluorescein isothiocyanate (FITC)-conjugated donkey antirabbit IgG and indocarbocyanine (Cy3; rhodamine)-conjugated donkey antimouse IgG were used to differentiate localization of the enzyme forms. Immunofluorescence of FITC and Cy3 was examined in prostate sections by using epifluorescence and confocal laser-scanning microscopy. Because fluorescence is dependent on section thickness, time needed for study and photography, and the antigenic sites of proCB and mature CB localized by antibodies and by fluorescent markers (Cy3 vs. FITC), the cellular distributions and the relative intensity of fluorescence on cryostat sections were assessed qualitatively. Immunofluorescence of Cy3 for localizing proCB and of FITC for localizing mature CB were observed in prostatic epithelial cells and their tumors and in stromal connective tissue cells. By using confocal microscopy, colocalization of the enzyme forms in the same cells was indicated by yellow fluorescence. In stromal cells (such as smooth muscles, fibroblast, and macrophages), the distribution of proCB and relative fluorescence intensity was moderate to predominant in human prostate and its tumors. In neoplastic prostate, the cellular distributions of CB ranged from low to predominant

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Section: Discussionsupporting

confidence: 90%

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

et al. 1998

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“…As shown in Figure 3A, AA increased endothelial cell migration by 70% to 80%, a level comparable to that of bFGF but less than VEGF. This observation is consistent with the report that VEGF is a stronger chemotactic factor than bFGF 31 Because mobilization of AA has been observed in endothelial cells on stimulation with angiogenic factors such as VEGF, 32 bFGF, 33 and angiogenin, 34 we studied the effect of various inhibitors of arachidonic acid metabolism on endothelial cell migration stimulated by VEGF. As shown in Figure 3B, ETYA, a promiscuous inhibitor for AA metabolism, inhibited VEGF-stimulated RV-ECT migration.…”

Section: Involvement Of Endogenous 12-lipoxygenase In Endothelial Celsupporting

confidence: 84%

Phase I Bioactive Lipids: Role in Prostate Cancer Angiogenesis""

Honn¹

2000

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the daia needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Manaqement and Budqet, ABSTRACT (Maximum 200 Words)The goal of DAMD17-98-1-8502 Idea Development Award is to investigate the role of 12-lipoxygenase (LOX) and its arachidonate product, 12(S)-hydroxyeicosatetraenoic acid (HETE), in human prostate cancer angiogenesis. The research progress during the funding period confirms the role of 12-LOX as a novel "angiogenic switch" governing prostate cancer angiogenesis and tumor growth. We found that 12-LOX increased the angiogenic potential of PCa cells by stimulating the production of VEGF, in addition to its arachidonate product 12(S)-HETE. The link between 12-LOX, a free fatty acid metabolizing enzyme, and VEGF, a putative angiogenic factor, is both novel and exciting, providing significant insights into our understanding of the regulation of VEGF expression during PCa progression. The study also found that 12-LOX and its lipid product, 12(S)-HETE, regulate VEGF expression at transcriptional level. The study also demonstrated the plausibility of using 12-LOX inhibitors such as BMD188 to inhibit prostate tumor angiogenesis and growth.14. SUBJECT INTRODUCTIONThe goal of DAMD17-98-1-8502 Idea Development Award is to investigate the role of 12-lipoxygenäse (LOX) and its arachidonate product, 12(S)-hydroxyeicosatetraenoic acid (HETE), in human prostate cancer angiogenesis. In the first 18-month funding period, we found that 12-LOX, when constitutively expressed in PC-3 cells, increased the ability of cancer cells to stimulate endothelial cell migration in vitro and angiogenesis in vivo and the ability to form larger, rapidly growing tumors in an animal model. Further it was found that 12-LOX functions as an "angiogenic switch" in PCa cells by stimulating the production of 12(S)-HETE and vascular endothelial growth factor (VEGF). 12(S)-HETE activates p42/44 MAP kinase in endothelial cells and stimulates endothelial cell migration. Further, 12(S)-HETE enhances the secretion of VEGF in PC-3 cells. Increased VEGF gene expression in 12-LOX transfected PC-3 cells was confirmed by ELISA measurement of VEGF levels, Northern Blot and VEGF promoter activity analysis. These observations, made in the first 18-month of funding, support our hypothesis that 12-LOX play a contributory role in prostate cancer angiogenesis. The findings also significantly further our understanding of prostate cancer angiogenesis in general and lipid regulation of angiogenesis in particular. The finding...

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“…Whereas the delayed mortality of the latter mice was primarily the result of the primary tumor burden, mice inoculated with cells expressing the secreted enzyme succumb because of liver metastases and dysfunction. The significance of cell surface localization and secretion of ECM-degrading enzymes in cancer metastasis was demonstrated by showing a correlation between the metastatic potential of breast and bladder carcinoma cells and translocation of cathepsins D and B from within lysosomes to the plasma membrane (39,40). In support of these observations are our recent results showing a markedly increased lung colonization of B16-F1 mouse melanoma cells that were first incubated with recombinant pro-heparanase, washed free of the unbound enzyme, and then inoculated into the tail vein of mice.…”

Section: Discussionmentioning

confidence: 99%

Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis

Goldshmidt

Zcharia

Abramovitch

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

157

160

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11 Alterations in Processing and Trafficking of Cathepsin B during Malignant Progression

Cited by 18 publications

References 0 publications

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

Phase I Bioactive Lipids: Role in Prostate Cancer Angiogenesis""

Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis

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