ArticleThe Journal of cell biology2003
A clathrin/dynamin- and mannose-6-phosphate receptor-independent pathway for granzyme B-induced cell death.
Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 106 citations in OpenAlex.
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- Dual Targeting of Cancer Cells and MMPs with Self-Assembly Hybrid Nanoparticles for Combination Therapy in Combating Cancer.Pharmaceutics · 2021Article
- The potential of CAR T cell therapy for prostate cancer.Nature reviews. Urology · 2021Review
- Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer.International journal of molecular sciences · 2020Review
- Solid Tumors Challenges and New Insights of CAR T Cell Engineering.Stem cell reviews and reports · 2019Review
- Combination therapy: A feasibility strategy for CAR-T cell therapy in the treatment of solid tumors.Oncology letters · 2018Review
- Granzyme B deficiency promotes osteoblastic differentiation and calcification of vascular smooth muscle cells in hypoxic pulmonary hypertension.Cell death & disease · 2018Article
- Radiation-induced autophagy potentiates immunotherapy of cancer via up-regulation of mannose 6-phosphate receptor on tumor cells in mice.Cancer immunology, immunotherapy : CII · 2014Article
- Novel mechanism of synergistic effects of conventional chemotherapy and immune therapy of cancer.Cancer immunology, immunotherapy : CII · 2013Review
- Autophagy induced by conventional chemotherapy mediates tumor cell sensitivity to immunotherapy.Cancer research · 2012Article
- Mechanism of synergistic effect of chemotherapy and immunotherapy of cancer.Cancer immunology, immunotherapy : CII · 2011Review
- Granzyme A activates another way to die.Immunological reviews · 2010Review
- Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice.The Journal of clinical investigation · 2010Article
- Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 280-kD cation-independent mannose-6-phosphate receptor (MPR) has been shown to play a role in endocytic uptake of granzyme B, since target cells overexpressing MPR have an increased sensitivity to granzyme B-mediated apoptosis. On this basis, it has been proposed that cells lacking MPR are poor targets for cytotoxic lymphocytes that mediate allograft rejection or tumor immune surveillance. In the present study, we report that the uptake of granzyme B into target cells is independent of MPR. We used HeLa cells overexpressing a dominant-negative mutated (K44A) form of dynamin and mouse fibroblasts overexpressing or lacking MPR to show that the MPR/clathrin/dynamin pathway is not required for granzyme B uptake. Consistent with this observation, cells lacking the MPR/clathrin pathway remained sensitive to granzyme B. Exposure of K44A-dynamin-overexpressing and wild-type HeLa cells to granzyme B with sublytic perforin resulted in similar apoptosis in the two cell populations, both in short and long term assays. Granzyme B uptake into MPR-overexpressing L cells was more rapid than into MPR-null L cells, but the receptor-deficient cells took up granzyme B through fluid phase micropinocytosis and remained sensitive to it. Contrary to previous findings, we also demonstrated that mouse tumor allografts that lack MPR expression were rejected as rapidly as tumors that overexpress MPR. Entry of granzyme B into target cells and its intracellular trafficking to induce target cell death in the presence of perforin are therefore not critically dependent on MPR or clathrin/dynamin-dependent endocytosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.