Analysis of the interaction of procathepsin D activation peptide with breast cancer cells

Větvička, Václav; Větvičková, Jana; Hilgert, I; Vobůrka, Zdeněk; Fusek, Martin

doi:10.1002/(sici)1097-0215(19971104)73:3<403::aid-ijc15>3.0.co;2-d

Cited by 53 publications

(62 citation statements)

References 22 publications

(16 reference statements)

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“…Using technique originally developed for staining intracellular cytokines, we showed not only the presence of pCD inside tumor cells, but also a significant increase of pCD staining when cells were incubated with the protein transport inhibitor brefeldin A. 56 Identical results were obtained when monensin, instead of brefeldin A, was used. The specificity of this secretion was shown by double staining with anti -MUCIN-1 mAb, which specifically stained breast cancer cells.…”

Section: Cancer Gene Therapymentioning

confidence: 72%

“…Additional experiments showed the presence of saturable, M6P-independent binding sites. 78 The proofs of the new pathway of pCD interaction with cell membrane were further strengthened by the finding that the binding of FITC-labeled pCD to cancer cells can be inhibited by unlabeled procathepsin but only marginally by either M6P, anti -M6P-R antibodies, or by soluble M6P-R. 56,79 In addition, the biological activities of pCD cannot be blocked by anti -M6P-R antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…48 The effects of various concentrations of either pCD or APpCD on proliferation of various breast cancer cells lines were described. 53,56 When growth factor activity of these molecules was evaluated, irrelevant synthetic peptides with similar purity and molecular weight (peptide representing the intracellular part of CR3 receptor and pig pepsinogen A) were used. 47 The optimal concentration of APpCD was found to be around 50 ng/mL, a dose slightly higher than required for the parent pCD molecule.…”

Section: Discussionmentioning

confidence: 99%

“…48 All these results suggested that the mitogenic function of activation peptide was mediated through a specific receptor expressed on all eight human breast cancer cell lines examined. Scatchard plot analysis revealed that the number of binding sites was 1.83Â10 4 per cell, with a K d of 0.61 nM 56 Next we prepared 10 synthetic peptides representing several parts of the activation peptide and compared their mitogenic activity. Our data indicated that the binding site of APpCD is located somewhere between amino acid positions 27 and 44 47,56 All peptides representing first 1 -27 AA of the APpCD peptide were not effective (Fig 4); AA 27 -44 peptide was effective at similar doses to those found with the APpCD.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

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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: Cancer Gene Therapymentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cancer Gene Therapymentioning

confidence: 99%

See 2 more Smart Citations

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

2002

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“…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. Our earlier studies established that pCD exerts mitogenic activity through interaction of its activation peptide (AP, propeptide) with an unknown receptor on cancer cells .…”

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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Role of procathepsin D activation peptide in prostate cancer growth

2000

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Analysis of the interaction of procathepsin D activation peptide with breast cancer cells

Cited by 53 publications

References 22 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

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

Role of procathepsin D activation peptide in prostate cancer growth

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