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

Jedd M. Hillegass, Arti Shukla, Sherrill A. Lathrop, Maximilian B. MacPherson, Stacie L. Beuschel, Kelly J. Butnor, Joseph R. Testa, Harvey I. Pass, Michele Carbone, Chad Steele, Brooke T. Mossman

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

80 Scopus citations

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.

Original languageEnglish
Title of host publicationOxidative/Nitrosative Stress and Disease
PublisherBlackwell Publishing Inc.
Pages7-14
Number of pages8
ISBN (Print)9781573317849
DOIs
StatePublished - Aug 2010

Publication series

NameAnnals of the New York Academy of Sciences
Volume1203
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • asbestos
  • chemokines
  • cytokines
  • inflammation
  • mesothelioma

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