ArticleThe American journal of pathology2003
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.
Article in The American journal of pathology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 94 citations in OpenAlex.
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms.Biomedicines · 2025Article
- Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells.Cell death & disease · 2023Article
- Tau Protein Interaction Partners and Their Roles in Alzheimer's Disease and Other Tauopathies.International journal of molecular sciences · 2021Review
- Endosomes, lysosomes, and the role of endosomal and lysosomal biogenesis in cancer development.Molecular biology reports · 2020Review
- CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands.International journal of molecular sciences · 2020Review
- Elevated Baseline Salivary Protease Activity May Predict the Steadiness of Gingival Inflammation During Periodontal Healing: A 12-Week Follow-Up Study on Adults.Pathogens (Basel, Switzerland) · 2020Article
- Proprotein convertases: Key players in inflammation-related malignancies and metastasis.Cancer letters · 2020Review
- Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies.Journal for immunotherapy of cancer · 2019Article
- Chemokines as adjuvants for immunotherapy: implications for immune activation with CCL3.Expert review of clinical immunology · 2017Review
- Mechanisms of Regulation of the Chemokine-Receptor Network.International journal of molecular sciences · 2017Review
- Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells.Cytotechnology · 2017Article
- A novel dual-targeted ultrasound contrast agent provides improvement of gene delivery efficiency in vitro.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Cathepsin D inhibitors as potential therapeutics for breast cancer treatment: Molecular docking and bioevaluation against triple-negative and triple-positive breast cancers.Molecular diversity · 2016Article
- The Potential Role of the Proteases Cathepsin D and Cathepsin L in the Progression and Metastasis of Epithelial Ovarian Cancer.Biomolecules · 2015Review
- Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma.British journal of cancer · 2015Article
- Yeast as a tool to explore cathepsin D function.Microbial cell (Graz, Austria) · 2015Review
- Quantitative proteomic analysis of single or fractionated radiation-induced proteins in human breast cancer MDA-MB-231 cells.Cell & bioscience · 2015Article
- Many Roles of CCL20: Emphasis on Breast Cancer.Postdoc journal : a journal of postdoctoral research and postdoctoral affairs · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1 alpha and MIP-1 beta degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu(58) to Trp(59) bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1 beta hybrids indicated that processing of MIP-1 beta might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1 alpha, MIP-1 beta, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes.
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