Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model

Ann N Y Acad Sci. 2010 Aug;1203:7-14. doi: 10.1111/j.1749-6632.2010.05554.x.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / chemistry
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / chemistry
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Cytokines / biosynthesis
  • Cytokines / chemistry
  • Cytokines / physiology
  • Disease Models, Animal
  • Fibrosarcoma / chemistry
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology
  • Humans
  • Inflammation Mediators / chemistry
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology*
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / physiology
  • Male
  • Mesothelioma / chemistry
  • Mesothelioma / metabolism
  • Mesothelioma / pathology*
  • Mice
  • Mice, SCID
  • Neutrophils / pathology
  • Pleural Neoplasms / chemistry
  • Pleural Neoplasms / metabolism
  • Pleural Neoplasms / pathology*
  • Protein Array Analysis
  • Time Factors
  • Xenograft Model Antitumor Assays* / methods

Substances

  • Cytokines
  • Inflammation Mediators
  • Intercellular Signaling Peptides and Proteins