Open AccessHistological sequence of the development of rat mesothelioma by MWCNT, with the involvement of apolipoproteins
Author(s) -
Hojo Motoki,
Yamamoto Yukio,
Sakamoto Yoshimitsu,
Maeno Ai,
Ohnuki Aya,
Suzuki Jin,
Inomata Akiko,
Moriyasu Takako,
Taquahashi Yuhji,
Kanno Jun,
Hirose Akihiko,
Nakae Dai
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14873
Subject(s) - mesothelioma , pathology , mesothelial cell , peritoneal mesothelioma , connective tissue , inflammation , carcinogenesis , medicine , infiltration (hvac) , biology , chemistry , cancer , immunology , materials science , composite material
A rat model of mesothelioma development by peritoneal injection of multiwalled carbon nanotube (MWCNT) has been established and found to be useful to understand the mechanisms underlying fibrous particles‐associated carcinogenesis. Its detailed histological sequence, however, remains largely obscure. We therefore aimed to assess the time‐course of mesothelioma development by MWCNT and evaluate a set of lipoprotein‐related molecules as potential mechanism‐based biomarkers for the phenomenon. Male Fischer 344 rats were injected intraperitoneally (ip) with MWCNT (MWNT‐7) at 1 mg/kg body weight, and necropsied at 8, 16, 24, 32, or 42 wk after injection. For biochemical analyses of the lipoprotein‐related molecules, more samples, including severe mesothelioma cases, were obtained from 2 other carcinogenicity tests. Histologically, in association with chronic inflammation, mesothelial proliferative lesions appeared at c . Wk‐24. Before and at the beginning of the tumor development, a prominent infiltration of CD163‐positive cells was seen near mesothelial cells. The histological pattern of early mesothelioma was not a papillary structure, but was a characteristic structure with a spherical appearance, composed of the mesothelioma cells in the surface area that were underlain by connective tissue‐like cells. Along with the progression, mesotheliomas started to show versatile histological subtypes. Serum levels of apolipoprotein A‐I and A‐IV, and a ratio of HDL cholesterol to total cholesterol were inversely correlated with mesothelioma severity. Overall, the detailed histological sequence of mesotheliomagenesis by MWCNT is demonstrated, and indicated that the altered profile of apolipoproteins may be involved in its underlying mechanisms.