Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model.
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.
Hillegass
Jedd M
JM
Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA.
Shukla
Arti
A
Lathrop
Sherrill A
SA
MacPherson
Maximilian B
MB
Beuschel
Stacie L
SL
Butnor
Kelly J
KJ
Testa
Joseph R
JR
Pass
Harvey I
HI
Carbone
Michele
M
Steele
Chad
C
Mossman
Brooke T
BT
D000818:Animals; D002277:Carcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D008297:Male; D008654:Mesothelioma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009504:Neutrophils / Q000473:pathology; D010997:Pleural Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D040081:Protein Array Analysis; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D016207:Cytokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins