ArticleOncotarget2016
Anti-metastatic potential of somatostatin analog SOM230: Indirect pharmacological targeting of pancreatic cancer-associated fibroblasts.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- The emerging role of chemokines and chemokine receptors in the biological and clinical behaviour of pituitary neuroendocrine tumours: An exploratory transcriptomic study.Journal of neuroendocrinology · 2026Article
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- Hydrogel-Based Therapeutics for Pancreatic Ductal Adenocarcinoma Treatment.Pharmaceutics · 2023Review
- Tumour microenvironment and pituitary tumour behaviour.Journal of endocrinological investigation · 2023Review
- The Effects of Peptide Receptor Radionuclide Therapy on the Neoplastic and Normal Pituitary.Cancers · 2023Review
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- Regulation of epithelial-mesenchymal transition by tumor microenvironmental signals and its implication in cancer therapeutics.Seminars in cancer biology · 2023Review
- The microenvironment of pituitary adenomas: biological, clinical and therapeutical implications.Pituitary · 2022Review
- Utilization of macrocyclic peptides to target protein-protein interactions in cancer.Frontiers in oncology · 2022Review
- Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?Cancers · 2021Review
- Role of cancer-associated fibroblast subpopulations in immune infiltration, as a new means of treatment in cancer.Immunological reviews · 2021Review
- Heart failure as interstitial cancer: emergence of a malignant fibroblast phenotype.Nature reviews. Cardiology · 2020Review
- GPCRs in pancreatic adenocarcinoma: Contributors to tumour biology and novel therapeutic targets.British journal of pharmacology · 2020Review
- Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression.International journal of molecular sciences · 2019Review
- Octreotide Nanoparticles Showed Affinity for In Vivo MIA Paca-2 Inducted Pancreas Ductal Adenocarcinoma Mimicking Pancreatic Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma).Pharmaceutical research · 2019Article
- Turning foes to friends: targeting cancer-associated fibroblasts.Nature reviews. Drug discovery · 2019Review
- International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.Pharmacological reviews · 2018Review
- Octreotide Does Not Inhibit Proliferation in Five Neuroendocrine Tumor Cell Lines.Frontiers in endocrinology · 2018Article
- Interferon-γ and Colorectal Cancer: an up-to date.Journal of Cancer · 2018Review
- Pasireotide is more effective than octreotide, alone or combined with everolimus on human meningiomaOncotarget · 2017Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDA) shows a rich stroma where cancer-associated fibroblasts (CAFs) represent the major cell type. CAFs are master secretors of proteins with pro-tumor features. CAF targeting remains a promising challenge for PDA, a devastating disease where treatments focusing on cancer cells have failed. We previously introduced a novel pharmacological CAF-targeting approach using the somatostatin analog SOM230 (pasireotide) that inhibits protein synthesis in CAFs, and subsequent chemoprotective features of CAF secretome. Using primary cultures of CAF isolated from human PDA resections, we here report that CAF secretome stimulates in vitro cancer cell survival, migration and invasive features, that are abolished when CAFs are treated with SOM230. Mechanistically, SOM230 inhibitory effect on CAFs depends on the somatostatin receptor subtype sst1 expressed in CAFs but not in non-activated pancreatic fibroblasts, and on protein synthesis shutdown through eiF4E-Binding Protein-1 (4E-BP1) expression decrease. We identify interleukin-6 as a SOM230-inhibited CAF-secreted effector, which stimulates cancer cell features through phosphoinositide 3-kinase activation. In vivo, mice orthotopically co-xenografted with the human pancreatic cancer MiaPaCa-2 cells and CAFs develop pancreatic tumors, on which SOM230 treatment does not inhibit growth but abrogates metastasis. Consistently, CAF secretome stimulates epithelial-to-mesenchymal transition in cancer cells, which is reversed upon CAF treatment with SOM230. Our results highlight a novel promising anti-metastatic potential for SOM230 indirectly targeting pancreatic cancer cell invasion through pharmacological inhibition of stromal CAFs.
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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.