Background: Locomotion of cancer cells can be induced by TNF and other motogenic factors secreted by cells of the tumour microenvironment such as macrophages. Based on our recent findings that the TNF receptor adaptor protein FAN mediates TNF-induced actin reorganisation and regulates the directed migration of immune cells responding to chemotactic cues, we addressed the role of FAN in cancer cell motility and the formation of invadopodia, a crucial feature in tumour invasion.
Methods: In B16 mouse melanoma cells, FAN was downregulated and the impact on FAN on cell motility and invasion was determined using in vitro assays and in vivo animal models.
Results: Like FAN(-/-) murine embryonic fibroblasts, FAN-deficient B16 melanoma cells showed defective motility responses to TNF in vitro. In vivo FAN-deficient B16 melanoma cells produced significantly less disseminated tumours after i.v. injection into mice. Danio rerio used as a second in vivo model also revealed impaired spreading of FAN-deficient B16 melanoma cells. Furthermore, FAN mediated TNF-induced paxillin phosphorylation, metalloproteinase activation and increased extracellular matrix degradation, the hallmarks of functionally active invadopodia.
Conclusion: The results of our study suggest that FAN through promoting melanoma cellular motility and tumour invasiveness is critical for the tumour-promoting action of TNF.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721409 | PMC |
| http://dx.doi.org/10.1038/bjc.2013.242 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Total Synthesis of Antiausterity Agent Callistrilone O Reveals Promising Antitumor Activity in a Melanoma Homograft Mouse Model.
ChemMedChem
January 2025
Kobe Pharmaceutical University: Kobe Yakka Daigaku, Laboratory of Microbial Chemistry, 4-19-1 Motoyamakita, Higashinada, 6588558, Kobe, JAPAN.
The antiausterity strategy in anticancer drug discovery has attracted much attention as a way to exterminate cancer cells under nutrient deprived conditions which are commonly found in solid tumors. These tumors under low nutrient stress are known to be malignant and often resist conventional drug therapy. As a potential drug candidate, we focused on the meroterpenoid natural product callistrilone O which has demonstrated extremely potent antiausterity properties toward PANC-1 pancreatic carcinoma in vitro.
View Article and Find Full Text PDFRecommendations of Multiple Sclerosis and Neuroimmunology Section of Polish Neurological Society and Immuno-oncology Section of Polish Society of Oncology on oncological risk in patients with multiple sclerosis undergoing immunomodulatory therapy.
Neurol Neurochir Pol
January 2025
Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Katowice, Poland.
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) that is usually diagnosed between the ages of 20 and 40. Changes in the immune system also observed in cancer may suggest a higher prevalence of cancer in the MS patient population. In recent years, many highly effective immunosuppressive drugs have been introduced into disease-modifying therapy (DMT) which may be associated with a higher risk of cancer development in patients with MS.
View Article and Find Full Text PDFNeoadjuvant Intratumoral MBT(A) Immunotherapy Prevents Distant Metastases and Recurrence in Murine Models.
Cancer Lett
January 2025
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA. Electronic address:
Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, offering novel avenues for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and antiCD40 antibody (MBTA therapy) followed by surgery in murine models of mouse tumor tissue (MTT) pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas.
View Article and Find Full Text PDFTumor Vaccine Exploiting Membranes with Influenza Virus-Induced Immunogenic Cell Death to Decorate Polylactic Coglycolic Acid Nanoparticles.
ACS Nano
January 2025
Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650031, China.
Immunogenic cell death (ICD) of tumor cells, which is characterized by releasing immunostimulatory "find me" and "eat me" signals, expressing proinflammatory cytokines and providing personalized and broad-spectrum tumor antigens draws increasing attention in developing a tumor vaccine. In this study, we aimed to investigate whether the influenza virus (IAV) is efficient enough to induce ICD in tumor cells and an extra modification of IAV components such as hemeagglutinin (HA) will be helpful for the ICD-induced cells to elicit robust antitumor effects; in addition, to evaluate whether the membrane-engineering polylactic coglycolic acid nanoparticles (PLGA NPs) simulating ICD immune stimulation mechanisms hold the potential to be a promising vaccine candidate, a mouse melanoma cell line (B16-F10 cell) was infected with IAV rescued by the reverse genetic system, and the prepared cells and membrane-modified PLGA NPs were used separately to immunize the melanoma-bearing mice. IAV-infected tumor cells exhibit dying status, releasing high mobility group box-1 (HMGB1) and adenosine triphosphate (ATP), and exposing calreticulin (CRT), IAV hemeagglutinin (HA), and tumor antigens like tyrosinase-related protein 2 (TRP2).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!