Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview

Rochefort, Henri; Garcia, Marcel; Glondu, Murielle; Laurent, V.; Liaudet, Emmanuelle; Rey, Jean-Marc; Roger, Pascal

doi:10.1016/s0009-8981(99)00226-0

Cited by 130 publications

(76 citation statements)

References 45 publications

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“…Later reviews discussed the possible dual role of (pro)cathepsin D in cancer development -acting as a protease after its activation and/or as a ligand on membrane receptor before activation. 10,12 Secreted pCD might be activated by acidic extracellular conditions and subsequently degrade growth inhibitors and extracellular matrix, or liberate some growth factors. The possibility of the extracellular matrix degradation seems to be supported by findings of Briozzo et al, 68 but their experiments showing liberation of FGF 2 from extracellular matrix are rather difficult to interpret.…”

Section: Discussionmentioning

confidence: 99%

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

2002

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Procathepsin D (pCD) is a major secreted glycoprotein in some human breast and other cancer cell lines. Several groups proposed that pCD served as a growth factor for these cell lines. Secreted pCD has been demonstrated in tissue section, tissue culture supernatants, carcinoma cytosols, and nipple aspirates. Moreover, several clinical studies suggested a potential role for this molecule in metastasis because its concentration in primary tumors correlated with an increased incidence of tumor metastases. In this paper, the effects of pCD were evaluated by proliferation in vitro and by mouse studies in vivo. Subsequent flow cytometry experiments showed the specificity of pCD binding to cancer cells. Cell cultivation showed that addition of either pCD or its activation peptide stimulates growth of cancer cells. These effects can be inhibited both in vitro and in vivo by anti-pCD antibodies. In addition, production of pCD can be inhibited by specifically designed ribozymes. This paper is focused on mitogenic effects of pCD, which seem to involve interaction of the activation peptide with as yet unidentified receptor. Different mechanisms by which pCD could promote development and spread of cancer cells are discussed.

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Section: Discussionmentioning

confidence: 99%

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

2002

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“…WEB-2086 reduced breast cancer cell mobility and active cathepsin D levels MDA-MB-231, unlike MCF-7, are cells with high mobility and have been used, therefore, to monitor WEB-2086 effects on cell migration and cathepsin D levels which associate closely with breast cancer invasiveness (Rochefort et al, 2000). Results of Boyden's chamber experiments ( Figure 4A) showed that a 5-day incubation of MDA-MB-231 with 0.5 mM WEB-2086 decreased cell migration of approximately 75% while the low-migrating activity of MCF-7 was virtually unaffected by 1 mM drug.…”

Section: Response Of Mda-mb-231 Cells To Web-2086mentioning

confidence: 99%

Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086

et al. 2006

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WEB-2086 -an antagonist of platelet-activating factor receptor (PAFR) with known anti-inflammatory, antiangiogenic and antileukaemic properties -also proved to inhibit the proliferation in human solid tumour cell lines of different histology, and with much higher efficacy than in normal fibroblasts. A detailed analysis of WEB-2086 anticancer activity was then performed focusing on breast adenocarcinoma MCF-7 and MDA-MB-231 cells. WEB-2086-treated cells, either expressing (MCF-7) or unexpressing (MDA-MB-231) the oestrogen receptor (ER)a, underwent a dose-dependent growth arrest (IC 50 ¼ 0.6570.09 and 0.4170.07 mM, respectively) and accumulation in G 0 -G 1 phase. WEB-2086 also induced morphological and functional changes typical of mature mammary phenotype including (i) cell enlargement and massive neutral lipid deposition (best accomplished in MCF-7 cells); (ii) decrease in motility and active cathepsin D levels (mainly observed in highly invasive MDA-MB-231 cells). The expression of ERa was neither increased nor reactivated in treated MCF-7 or MDA-MB-231 cells, respectively. WEB-2086-induced differentiation in breast cancer cells involved the upregulation of PTEN, a key tumour suppressor protein opposing tumorigenesis, and was apparently independent of p53, PAFR, peripheral benzodiazepine receptor and ERa status. Overall, WEB-2086 can be proposed as an effective antiproliferative and differentiative agent with interesting translational opportunities to treat breast cancers in support to conventional chemotherapy.

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“…Increased levels of procathepsin D (pCD), proform of CD, and/or CD are correlated with tumor cell invasion and metastasis in breast carcinoma (Rochefort et al, 2000). It is now well established that the secreted pCD promotes growth of cancer cells (Stewart et al, 1994;Vetvicka et al, 1994Vetvicka et al, , 1997.…”

Section: Introductionmentioning

confidence: 99%

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta¹,

Ohri²,

Větvičková³

et al. 2007

European Journal of Cell Biology

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Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is overexpressed and secreted by various carcinomas. The fact that secreted pCD plays an essential role in progression of cancer has been established. In this study, we describe substantial secretion of pCD by the human keratinocyte cell line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD was inhibited by a monoclonal antibody against the activation peptide (AP) of pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of cytokines that might promote the growth of cells in a paracrine manner. The role of secreted pCD and its mechanism of action were studied in a scratch wound model and the presence of pCD and AP enhanced regeneration, while this effect was reversed by the addition of anti-AP antibody. Expression and secretion of pCD was upregulated in HaCaT cells exposed to various stress conditions. Taken together, our results strongly suggest that the secretion of pCD is not only linked to cancer cells but also plays a role in normal physiological conditions like wound healing and tissue remodeling.

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Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview

Cited by 130 publications

References 45 publications

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086

Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

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