Oncogene  2002 Jul 11;21(30):4646-62 

Novel colon cancer cell lines leading to better understanding of the diversity
of respective primary cancers.

Vecsey-Semjen B, Becker KF, Sinski A, Blennow E, Vietor I, Zatloukal K, Beug H,
Wagner E, Huber LA.

IMP, Research Institute of Molecular Pathology, Vienna, Austria.

A major obstacle to obtaining more detailed insights into the diversity of
phenotypic and molecular changes occurring in colon cancer cells is the lack of
low-passage colon cancer cell lines, which would still closely reflect the
phenotype of the colon cancer cells in vivo. Here, we characterize eight novel,
low passage number human colon carcinoma cell lines, originating from colorectal
cancers extensively characterized in the clinics. All cell lines closely
resemble the original tumors with respect to phenotype, markers and detectable
genetic changes. Cell morphology and marker expression is highly variable,
ranging from fully polarized cells correctly expressing all basolateral
epithelial markers, to cells with mesenchymal characteristics and a complete
loss of polarity due to delocalization or loss of junction complex proteins. The
alterations in phenotype and epithelial marker expression correspond to changes
already detectable in the primary tumor in vivo. Seven of the cell lines show
chromosomal instability, while one cell line is characterized by microsatellite
instability. p53 associated with K-ras mutations were detected in three cell
lines. Hitherto non-described E-cadherin mutations were found at both alleles in
one cell line whereas in another cell line the E-cadherin protein was
down-regulated. A stabilizing beta-catenin mutation (S45F) appears in the same
cell line that carried the mutated E-cadherin gene. Six cell lines carried APC
mutations, which in five of the lines led to an activated beta-catenin/Tcf/LEF
signaling pathway. In accordance with beta-catenin/Tcf/LEF activation, the cell
lines show increased migration and invasiveness. Our results show that the
characterized, low-passage cell lines mirror the diversity of the individual
tumors from which they were derived. Through molecular analyses of these cell
lines we demonstrate that tumorgenicity events are much more diverse in human
colon cancer than expected, despite the common origin of the tumors from a small
patient group with similar tumor grading and clinical prognosis.

PMID: 12096341 [PubMed - indexed for MEDLINE]