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Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model
Published on: October 2, 2015
Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model
Jedd M Hillegass1, Arti Shukla, Sherrill A Lathrop
1Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA.
Abstract:
Asbestos fibers cause chronic inflammation that may be critical to the development of malignant mesothelioma (MM). Two human MM cell lines (Hmeso, PPM Mill) were used in a SCID mouse xenograft model to assess time-dependent patterns of inflammation and tumor formation. After intraperitoneal (IP) injection of MM cells, mice were euthanized at 7, 14, and 30 days, and peritoneal lavage fluid (PLF) was examined for immune cell profiles and human and mouse cytokines. Increases in human MM-derived IL-6, IL-8, bFGF, and VEGF were observed in mice at 7 days postinjection of either MM line, and a striking neutrophilia was observed at all time points. Free-floating tumor spheroids developed in mice at 14 days, and both spheroids and adherent MM tumor masses occurred in all mice at 30 days. Results suggest that inflammation and cytokine production precede and may be critical to the development of MMs.
Insights
Chronic inflammation and cytokine release precede malignant mesothelioma (MM) development. This study in mice shows that immune responses and tumor growth are closely linked, suggesting inflammation is critical for MM formation.
Area of Science:
- Oncology
- Immunology
- Toxicology
Background:
- Asbestos exposure is a known cause of malignant mesothelioma (MM).
- Chronic inflammation is implicated in the pathogenesis of MM.
- The early events linking asbestos-induced inflammation to MM development require further elucidation.
Purpose of the Study:
- To investigate the temporal relationship between inflammation and tumor formation in a mouse model of malignant mesothelioma.
- To characterize immune cell profiles and cytokine production following MM cell implantation.
Main Methods:
- Two human MM cell lines (Hmeso, PPM Mill) were xenografted into SCID mice via intraperitoneal injection.
- Mice were euthanized at 7, 14, and 30 days post-injection.
- Peritoneal lavage fluid (PLF) was analyzed for immune cell counts and cytokine levels (IL-6, IL-8, bFGF, VEGF).
Main Results:
- Elevated levels of human MM-derived cytokines (IL-6, IL-8, bFGF, VEGF) were detected by day 7.
- A significant increase in neutrophils (neutrophilia) was observed at all time points.
- Free-floating tumor spheroids appeared by day 14, with adherent tumor masses present in all mice by day 30.
Conclusions:
- Inflammation and elevated cytokine production occur early in the development of MM in this model.
- These inflammatory processes precede and may be critical drivers of MM tumor formation.
- The findings highlight the role of the inflammatory microenvironment in MM pathogenesis.
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