PloS one, 2017-06, Vol.12 (6), p.e0179862-e0179862
2017
Details
- Autor(en) / Beteiligte
- Titel
- Unique cellular interactions between pancreatic cancer cells and the omentum
- Ist Teil von
- PloS one, 2017-06, Vol.12 (6), p.e0179862-e0179862
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Pancreatic cancer is a common cause of cancer-related mortality. Omental spread is frequent and usually represents an ominous event, leading to patient death. Omental metastasis has been studied in ovarian cancer, but data on its role in pancreatic cancer are relatively scarce and the molecular biology of this process has yet to be explored. We prepared tissue explants from human omental fat, and used conditioned medium from the explants for various in vitro and in vivo experiments designed to evaluate pancreatic cancer development, growth, and survival. Mass spectrometry identified the fat secretome, and mRNA array identified specific fat-induced molecular alternations in tumor cells. Omental fat increased pancreatic cancer cellular growth, migration, invasion, and chemoresistance. We identified diverse potential molecules secreted by the omentum, which are associated with various pro-tumorigenic biological processes. Our mRNA array identified specific omental-induced molecular alternations that are associated with cancer progression and metastasis. Omental fat increased the expression of transcription factors, mRNA of extracellular matrix proteins, and adhesion molecules. In support with our in vitro data, in vivo experiments demonstrated an increased pancreatic cancer tumor growth rate of PANC-1 cells co-cultured for 24 hours with human omental fat conditioned medium. Our results provide novel data on the role of omental tissue in omental metastases of pancreatic cancer. They imply that omental fat secreted factors induce cellular reprogramming of pancreatic cancer cells, resulting in increased tumor aggressiveness. Understanding the mechanisms of omental metastases may enable us to discover new potential targets for therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0179862Titel-ID: cdi_plos_journals_1911588120
- Format
- –
- Schlagworte
- Adhesion, Adipocytes, Adipocytes - cytology, Adipocytes - metabolism, Alternations, Animals, Antigens, Antimetabolites, Antineoplastic - toxicity, Apoptosis, Apoptosis - drug effects, Biological activity, Biology and Life Sciences, Cancer, Cancer cells, Cancer therapies, Cell Cycle Checkpoints - drug effects, Cell growth, Cell Movement - drug effects, Cell Proliferation - drug effects, Cells, Cultured, Chemoresistance, Chromatography, High Pressure Liquid, Conditioning, Culture Media, Conditioned - analysis, Culture Media, Conditioned - metabolism, Culture Media, Conditioned - pharmacology, Death, Deoxycytidine - analogs & derivatives, Deoxycytidine - toxicity, Development and progression, Explants, Extracellular matrix, Gene expression, Genetic aspects, Growth rate, Health aspects, Humans, Immunohistochemistry, In vitro methods and tests, Male, Mass spectrometry, Mass spectroscopy, Medical research, Medicine, Medicine and Health Sciences, Metastases, Metastasis, Mice, Mice, Nude, Molecular biology, Mortality, Omentum, Omentum - cytology, Ovarian cancer, Ovarian carcinoma, Pancreatic cancer, Pancreatic Neoplasms - metabolism, Pancreatic Neoplasms - pathology, Physiological aspects, Proteins, Rodents, Secretome, Surgery, Survival, Tandem Mass Spectrometry, Therapy, Transcription factors, Transplantation, Heterologous, Tumor cells, Vital signs