ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Targeted Proapoptotic Peptides Depleting Adipose Stromal Cells Inhibit Tumor Growth.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Fibulin-4 expressed in metastatic breast cancer is a target of peptide-based imaging probes and experimental therapeutics.Molecular therapy. Oncology · 2026Article
- Depletion of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy.Cancer research communications · 2025Article
- Lung cancer and obesity: A contentious relationship (Review).Oncology reports · 2024Review
- Adipocyte derived exosomes promote cell invasion and challenge paclitaxel efficacy in ovarian cancer.Cell communication and signaling : CCS · 2024Article
- Zinc-alpha-2-glycoprotein Secreted by Triple-Negative Breast Cancer Promotes Peritumoral Fibrosis.Cancer research communications · 2024Article
- Zinc Alpha-2-Glycoprotein (ZAG/AZGP1) secreted by triple-negative breast cancer promotes tumor microenvironment fibrosis.bioRxiv : the preprint server for biology · 2024Article
- New Insights into the Link Between Melanoma and Obesity.Advances in experimental medicine and biology · 2024Review
- Obesity and prostate cancer - microenvironmental roles of adipose tissue.Nature reviews. Urology · 2023Review
- White adipose tissue-derived factors and prostate cancer progression: mechanisms and targets for interventions.Cancer metastasis reviews · 2022Review
- Fatty acid translocase: a culprit of lipid metabolism dysfunction in disease.Immunometabolism (Cobham, Surrey) · 2022Review
- Biomedical polymers: synthesis, properties, and applications.Science China. Chemistry · 2022Review
- Partial Ablation of Non-Myogenic Progenitor Cells as a Therapeutic Approach to Duchenne Muscular Dystrophy.Biomolecules · 2021Article
- Fatty acid mobilization from adipose tissue is mediated by CD36 posttranslational modifications and intracellular trafficking.JCI insight · 2021Article
- Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue.Nature communications · 2021Article
- Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium.NPJ precision oncology · 2021Article
- Glycosaminoglycan Modification of Decorin Depends on MMP14 Activity and Regulates Collagen Assembly.Cells · 2020Article
- PAI-1-Dependent Inactivation of SMAD4-Modulated Junction and Adhesion Complex in Obese Endometrial Cancer.Cell reports · 2020Article
- Ablation of Stromal Cells with a Targeted Proapoptotic Peptide Suppresses Cancer Chemotherapy Resistance and Metastasis.Molecular therapy oncolytics · 2020Article
- Identification and characterization of adipose surface epitopes.The Biochemical journal · 2020Review
- Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progression of many cancers is associated with tumor infiltration by mesenchymal stromal cells (MSC). Adipose stromal cells (ASC) are MSC that serve as adipocyte progenitors and endothelium-supporting cells in white adipose tissue (WAT). Clinical and animal model studies indicate that ASC mobilized from WAT are recruited by tumors. Direct evidence for ASC function in tumor microenvironment has been lacking due to unavailability of approaches to specifically inactivate these cells. Here, we investigate the effects of a proteolysis-resistant targeted hunter-killer peptide D-WAT composed of a cyclic domain CSWKYWFGEC homing to ASC and of a proapoptotic domain KLAKLAK2. Using mouse bone marrow transplantation models, we show that D-WAT treatment specifically depletes tumor stromal and perivascular cells without directly killing malignant cells or tumor-infiltrating leukocytes. In several mouse carcinoma models, targeted ASC cytoablation reduced tumor vascularity and cell proliferation resulting in hemorrhaging, necrosis, and suppressed tumor growth. We also validated a D-WAT derivative with a proapoptotic domain KFAKFAK2 that was found to have an improved cytoablative activity. Our results for the first time demonstrate that ASC, recruited as a component of tumor microenvironment, support cancer progression. We propose that drugs targeting ASC can be developed as a combination therapy complementing conventional cancer treatments.
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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 Socratic graph.