Transforming growth  factor beta production by spontaneous malignant mesothelioma cell lines derived from Fisher 344 rats.
We investigated whether transforming growth factor beta (TGF-beta) is involved in the growth of malignant mesothelioma (MM) cells in culture. TGF-beta production was examined in two mesothelioma cell lines (MeET-4 and -6) that were established from rat spontaneous MM in our laboratory. TGF-beta bioactivity in conditioned medium of these cell lines was analyzed using a CCL64 mink lung epithelial cell growth inhibition assay and found to be 30-70 times higher than that of normal rat mesothelial cells (MCs). The MM cell lines also showed considerably higher levels of TGF-beta mRNA expression when compared with MCs. The bioactivity and mRNA expression level were greater in MeET-4 than MeET-6. When MeET-4 was treated with antisense TGF-beta1 oligonucleotide (ODN), a significant decrease in both anchorage-dependent and -independent growth was observed. Treatment with exogenous TGF-beta resulted in no effects on the growth pattern of the MM cell lines, while proliferation of the MCs was slightly induced. It is considered that TGF-beta appears to be produced by rat spontaneous MM cells through an autocrine mechanism and could modulate the malignant growth of the tumor cells.
Kuwahara
M
M
Division II, The Institute of Environmental Toxicology, Mitsukaido-shi, Ibaraki, Japan. kuwahara@iet.ne.jp
Takeda
M
M
Takeuchi
Y
Y
Kuwahara
M
M
Harada
T
T
Maita
K
K
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010537:Peritoneum / Q000166:cytology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D012186:Retroperitoneal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000473:pathology
D017077:Culture Media, Conditioned; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta