Biological characteristics and chemosensitivity profile of four human anaplastic thyroid carcinoma cell lines.
Anaplastic thyroid carcinoma is a rapidly growing, aggressive neoplasm affecting the elderly which does not respond to most of the therapies. We established cultured cell lines from four untreated tumors. The cultures grew in a monolayer of spindle-shaped cells in three cell lines and of small polygonal cells in one line, having relatively long doubling times and chromosomal abnormalities. The xenotransplantation of the lines in athymic nude mice produced tumors with a histology similar to the original tumors. The immunocytochemical staining showed the expression of PCNA, HLA-class 1, cytokeratin, vimentin and FAS (fatty acid synthase) but not CEA, desmin or P-glycoprotein. The lines secreted TPA, IL-6, IL-8 and few or no thyroid-related hormones in the culture supernatant. One cell line produced G-CSF. The chemosensitivity assay revealed intrinsic drug resistance to nine out of 11 antineoplastic agents. The reverse transcriptase-polymerase chain reaction (RT-PCR) detected MRP (multidrug resistance-associated protein) mRNA but not mdr (multidrug resistance protein)-1 and mdr-3 mRNAs. This finding indicates that the multidrug resistance of these lines is mediated by a P-glycoprotein-unrelated mechanism. The RT-PCR also presented FAS mRNA in all the lines, and IL-6 and IL-8 mRNAs in some of the lines.
Sekiguchi
M
M
EIectro-Chemical and Cancer Institute, Chofu, Tokyo, Japan. m-sekiguchi@alpha-medic.gr.jp
Shiroko
Y
Y
Arai
T
T
Kishino
T
T
Sugawara
I
I
Kusakabe
T
T
Suzuki
T
T
Yamashita
T
T
Obara
T
T
Ito
K
K
Hasumi
K
K
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002869:Chromosome Aberrations; D019008:Drug Resistance, Neoplasm; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007621:Karyotyping; D007633:Keratins / Q000032:analysis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D019014:fas Receptor / Q000032:analysis
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; D016209:Interleukin-8; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D019014:fas Receptor; D007633:Keratins; C095122:multidrug resistance protein 3; D064429:Fatty Acid Synthases