A colorectal cell line with alterations in E-cadherin and epithelial biology may be an in vitro model of colitis.
BACKGROUND
It has been shown previously in ulcerative colitis tissue that E-cadherin can occasionally be mutated in the extracellular domain early in neoplastic progression. E-cadherin is known to maintain differentiation and inhibits invasion in vivo.


OBJECTIVE
To assess the mechanisms by which such dysfunction occurs.


METHODS
Four human colorectal cancer cell lines, HCA-7 colonies 1, 3, 6, and 30, derived from a single heterogeneous colorectal cancer were studied. The HCA-7 cell line has p53 mutations and a random errors of replication "positive" phenotype, as is seen in early colitis associated cancers or hereditary nonpolyposis coli cancer (HNPCC).


RESULTS
Cell lines 6 and 30 expressed E-cadherin abundantly and this correlated positively with their degree of differentiation and organisation; however, both cell lines had loss of heterozygosity of E-cadherin. Interestingly, E-cadherin production was downregulated in the poorly differentiated cell line 1, and this was associated with major chromosomal rearrangements of 16q. This cell line also had a mutation in the homophilic binding domain of exon 4, which was associated with disaggregation by low titres of a function blocking antibody, and an invasive phenotype.


CONCLUSIONS
These multiple biological alterations further characterise the complex association that E-cadherin has with tumour heterogeneity and suggest that this series of cell lines may be a useful model of colitis associated or HNPCC associated tumorigenesis.
Perry
I
I
Epithelial Laboratory, University of Birmingham, UK.
Hardy
R
R
Jones
T
T
Jankowski
J
J
D000362:Agar; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003094:Collagen; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003470:Culture Media; D006801:Humans; D007621:Karyotyping; D008954:Models, Biological; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D015820:Cadherins; D003470:Culture Media; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000362:Agar; D003094:Collagen