Cathepsin in rats with transplantable cancer

Purr, Arnulf

doi:10.1042/bj0281907

Cited by 23 publications

(4 citation statements)

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“…The possible link between cathepsins and cancer and the role of cathepsin B in metastatic potential was postulated since many years [ 30 , 31 ]. For instance, numerous clinical studies have hypothesized a correlation between extralysosomal cathepsin B expression and release with neoplastic disease progression and clinical outcome [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

et al. 2010

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BackgroundCathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness.ResultsIn the present work we first evaluated, by in vitro procedures, the role of cathepsins B, L and D, in the remodeling, spreading and invasiveness of eight different cell lines: four primary and four metastatic melanoma cell lines. Among these, we considered two cell lines derived from a primary cutaneous melanoma and from a supraclavicular lymph node metastasis of the same patient. To this purpose, the effects of specific chemical inhibitors of these proteases, i.e. CA-074 and CA-074Me for cathepsin B, Cathepsin inhibitor II for cathepsin L, and Pepstatin A for cathepsin D, were evaluated. In addition, we also analyzed the effects of the biological inhibitors of these cathepsins, i.e. specific antibodies, on cell invasiveness. We found that i) cathepsin B, but not cathepsins L and D, was highly expressed at the surface of metastatic but not of primary melanoma cell lines and that ii) CA-074, or specific antibodies to cathepsin B, hindered metastatic cell spreading and dissemination, whereas neither chemical nor biological inhibitors of cathepsins D and L had significant effects. Accordingly, in vivo studies, i.e. in murine xenografts, demonstrated that CA-074 significantly reduced human melanoma growth and the number of artificial lung metastases.ConclusionsThese results suggest a reappraisal of the use of cathepsin B inhibitors (either chemical or biological) as innovative strategy in the management of metastatic melanoma disease.

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Section: Discussionmentioning

confidence: 99%

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

et al. 2010

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“…AMP-001 spares normal cells from off-target effects, by releasing the drug near tumor sites and only activating upon the cleavage of its valine-citrulline link. This linkage is only cleavable by tumor-specific biomolecule Cathepsin B, which is highly upregulated by malignant tumors in comparison to normal tissues and becomes attached to the tumor surface [36], [37], [38], [39]. Furthermore, due to its pegylation AMP-001 is water soluble, enhancing it's by keeping it intact in blood circulation until reaching pertinent tumor cells [20], [21].…”

Section: Discussionmentioning

confidence: 99%

Targeted Sensitization of Glioblastoma Multiforme Using AAAPT Technology

Mendieta,

Avci,

Pandurangi

et al. 2023

IEEE Open J. Eng. Med. Biol.

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Glioblastoma Multiforme (GBM) is the most malignant type of all brain tumors. Current GBM treatment options include surgery, followed by radiation and chemotherapy. However, GBM can become resistant to therapy, resulting in tumor recurrence. GBM cells develop resistance to treatments by either downregulating cell death pathways (CD95) or upregulating cell survival pathways (NF-κB (p65)). Healthy tissues can be affected by the increased therapeutic dose. Therefore, it is important to develop a method that can only target GBM tumor cells, thereby reducing the non-specific uptake which will reduce the side effects. Here we demonstrate an application of novel priori activation of apoptosis pathways of tumor technology (AAAPT), which has been used to demonstrate the effect of targeted tumor sensitizers to make chemotherapy work at lower doses in breast, lung and prostate cancers. Treatment of GBM spheroids with AAAPT in 3D PEGDA microwells, showed an increase in cell death, an upregulation of cell death pathways, and a downregulation of cell survival pathways, in comparison to Temozolomide (TMZ), an oral alkylating agent, which is a commonly used chemotherapy in the treatment of GBM. The dose of AAAPT sensitizers may provide a promising method to increase treatment efficacy and reduce off-target toxicity, as an alternative to existing methods which cause significant off-target damage.

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“…AMP-001 spares normal cells from off-target effects, by releasing the drug near tumor sites and only activating upon the cleavage of its valinecitrulline link. This linkage is only cleavable by tumorspecific biomolecule Cathepsin B, which is highly upregulated by malignant tumors in comparison to normal tissues and becomes attached to the tumor surface [36], [37], [38], [39]. Furthermore, due to its pegylation AMP-001 is water soluble, enhancing it's by keeping it intact in blood circulation until reaching pertinent tumor cells [20], [21].…”

Section: Discussionmentioning

confidence: 99%

Targeted Sensitization of Glioblastoma Multiforme Using AAAPT Technology

Akay,

Mendieta,

Avci

et al. 2023

Preprint

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Cathepsin in rats with transplantable cancer

Cited by 23 publications

References 0 publications

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

Targeted Sensitization of Glioblastoma Multiforme Using AAAPT Technology

Targeted Sensitization of Glioblastoma Multiforme Using AAAPT Technology

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