Serum level of expressed in renal carcinoma (ERC)/ mesothelin in rats with mesothelial proliferative lesions induced by multi-wall carbon nanotube (MWCNT).
Expressed in renal carcinoma (ERC)/mesothelin is a good biomarker for human mesothelioma and has been investigated for its mechanistic rationale during the mesothelioma development. Studies are thus ongoing in our laboratories to assess expression of ERC/mesothelin in sera and normal/proliferative/neoplastic mesothelial tissues of animals untreated or given potentially mesothelioma-inducible xenobiotics, by an enzyme-linked immunosorbent assay (ELISA) for N- and C-(terminal fragments of) ERC/mesothelin and immunohistochemistry for C-ERC/mesothelin. In the present paper, we intend to communicate our preliminary data, because this is the first report to show how and from what stage the ERC/mesothelin expression changes during the chemical induction of mesothelial proliferative/neoplatic lesions. Serum N-ERC/mesothelin levels were 51.4 +/- 5.6 ng/ml in control male Fischer 344 rats, increased to 83.6 +/- 11.2 ng/ml in rats given a single intrascrotal administration of 1 mg/kg body weight of multi-wall carbon nanotube (MWCNT) and bearing mesothelial hyperplasia 52 weeks thereafter, and further elevated to 180 +/- 77 ng/ml in rats similarly treated and becoming moribund 40 weeks thereafter, or killed as scheduled at the end of week 52, bearing mesothelioma. While C-ERC/mesothelin was expressed in normal and hyperplastic mesothelia, the protein was detected only in epithelioid mesothelioma cells at the most superficial layer. It is thus suggested that ERC/mesothelin can be used as a biomarker of mesothelial proliferative lesions also in animals, and that the increase of levels may start from the early stage and be enhanced by the progression of the mesothelioma development.
Sakamoto
Yoshimitsu
Y
Dai
Nakae
N
Hagiwara
Yoshiaki
Y
Satoh
Kanako
K
Ohashi
Norio
N
Fukamachi
Katsumi
K
Tsuda
Hiroyuki
H
Hirose
Akihiko
A
Nishimura
Tetsuji
T
Hino
Okio
O
Ogata
Akio
A
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D058851:GPI-Linked Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D000090204:Mesothelin; D037742:Nanotubes, Carbon / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C000715529:Msln protein, rat; D037742:Nanotubes, Carbon; D000090204:Mesothelin