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  • Original Paper
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Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers

Oncogene volume 21, pages 4646–4662 (2002)Cite this article

Abstract

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 β-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 β-catenin/Tcf/LEF signaling pathway. In accordance with β-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.

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Abbreviations

aa:

amino acid

APC:

adenomatous polyposis coli

bp:

base pair

DMEM:

Dulbecco's Modified Eagle Medium

FCS:

fetal calf serum

LEF-1:

leukocyte enhancing factor

LOH:

loss of heterozygosity

nt:

nucleotide

PCR:

polymerase chain reaction

TCF:

T-cell factor

HNPCC:

hereditary non-polyposis colon cancer

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Acknowledgements

The authors thank C Schott for excellent technical assistance. We would also like to thank H Clevers (Utrecht University, The Netherlands) for pTOPFLASH and pFOPFLASH reporter constructs. The cooperation with Professor HJ Mischinger and Professor H Hauser (Department of Surgery, University of Graz), Professor P Steindorfer, Dr H Worschitz (2nd Department of Surgery, Landeskrankenhaus Graz), Professor A Berger and Dr G Seitinger (Department of Surgery, Hospital of the Bamherzigen Brüder, Graz), and Dr Ch Mörth (Institute of Pathology, University of Graz) in providing the tumor samples is gratefully acknowledged. Part of this work was supported by a grant from Wilhelm-Sander-Stiftung to KF Becker and a grant from the Österreichischen Krebshilfe Steiermark to K Zatloukal. Work in the Huber lab was supported by Boehringer Ingelheim and by a grant from the Vienna Industrial Promotion Fund (WWF, GZW 11106/99La).

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Author notes

  1. Ernst Wagner

    Present address: Department of Histology and Molecular Cell Biology, University of Innsbruck, Medical School, Muellerstrasse 59, Innsbruck, A-6020, Austria

  2. Lukas A Huber

    Present address: Pharmaceutical Biology - Biotechnology, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, Munich, D-81377, Germany

Authors and Affiliations

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

    Beatrix Vécsey-Semjén, Ilja Vietor, Hartmut Beug & Lukas A Huber

  2. Department of Pathology, TUM, Technical University of Munich, Munich and GSF-National Research Center for Environment and Health, Neuherberg, Germany

    Karl-Friedrich Becker

  3. Live Vaccine Division Vienna, BI, Boehringer Ingelheim Austria GmbH, Austria

    Alexandra Sinski & Ernst Wagner

  4. Department of Clinical Genetics, KS, Karolinska Hospital, Stockholm, Sweden

    Elizabeth Blennow

  5. Institute of Pathology, University of Graz, Austria

    Kurt Zatloukal

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Correspondence to Ernst Wagner or Lukas A Huber.

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Vécsey-Semjén, B., Becker, KF., Sinski, A. et al. Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers. Oncogene 21, 4646–4662 (2002). https://doi.org/10.1038/sj.onc.1205577

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