TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

• Published in: Scientific reports Vol. 8; no. 1; pp. 13231 - 17
• Main Authors: Granados-Soler, José Luis, Junginger, Johannes, Hewicker-Trautwein, Marion, Bornemann-Kolatzki, Kirsten, Beck, Julia, Brenig, Bertram, Betz, Daniela, Schille, Jan Torben, Murua Escobar, Hugo, Nolte, Ingo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-09-2018; Nature Publishing Group
• Subjects: 13/1; 13/31; 13/51; 45/77; 631/532/71; 631/67/1347; 631/80/84/2176; 692/4028/67/1347; 692/4028/67/69; 96/100; 96/2; AKT1 protein; Breast cancer; Breast carcinoma; CD44 antigen; Chromosomes; Cyclin-dependent kinase 4; Doxorubicin; GATA-3 protein; Humanities and Social Sciences; Mammary gland; Mesenchyme; multidisciplinary; Myc protein; Phenotypes; Physical characteristics; Science; Science (multidisciplinary); Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-31682-1

Feline mammary carcinomas (FMCs) with anaplastic and malignant spindle cells histologically resemble the human metaplastic breast carcinoma (hMBC), spindle-cell subtype. hMBCs display epithelial-to-mesenchymal transition (EMT) characteristics. Herein we report the establishment and characterization of a cell line (TiHoCMglAdcar0906; TiHo-0906) exhibiting EMT-like properties derived from an FMC with anaplastic and malignant spindle cells. Copy-number variations (CNVs) by next-generation sequencing and immunohistochemical characteristics of the cell line and the tumour were compared. The absolute qPCR expression of EMT-related markers
HMGA2
and
CD44
was determined. The growth, migration, and sensitivity to doxorubicin were assessed. TiHo-0906 CNVs affect several genomic regions harbouring known EMT-, breast cancer-, and hMBCs-associated genes as
AKT1
,
GATA3
,
CCND2
,
CDK4
,
ZEB1
,
KRAS
,
HMGA2
,
ESRP1
,
MTDH
,
YWHAZ
, and
MYC
. Most of them were located in amplified regions of feline chromosomes (FCAs) B4 and F2. TiHo-0906 cells displayed an epithelial/mesenchymal phenotype, and high
HMGA2
and
CD44
expression. Growth and migration remained comparable during subculturing. Low-passaged cells were two-fold more resistant to doxorubicin than high-passaged cells (IC50: 99.97 nM, and 41.22 nM, respectively). The TiHo-0906 cell line was derived from a poorly differentiated cellular subpopulation of the tumour consistently displaying EMT traits. The cell line presents excellent opportunities for studying EMT on FMCs.