A Complex of EpCAM, Claudin-7, CD44 Variant Isoforms, and Tetraspanins Promotes Colorectal Cancer Progression

• Published in: Molecular cancer research Vol. 5; no. 6; pp. 553 - 567
• Main Authors: Kuhn, Sebastian, Koch, Moritz, Nübel, Tobias, Ladwein, Markus, Antolovic, Dalibor, Klingbeil, Pamela, Hildebrand, Dagmar, Moldenhauer, Gerhard, Langbein, Lutz, Franke, Werner W, Weitz, Jürgen, Zöller, Margot
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-06-2007
• Subjects: Antigens, Neoplasm - physiology; Apoptosis; Cell Adhesion Molecules - physiology; Cell Line, Tumor; Claudin; Claudins; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - pathology; Disease Progression; Disease-Free Survival; EpCAM; Epithelial Cell Adhesion Molecule; Humans; Hyaluronan Receptors - physiology; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Membrane Glycoproteins - physiology; Membrane Microdomains - chemistry; Membrane Proteins - physiology; Metastasis; Neoplasm Metastasis; Protein Isoforms; Tetraspanin-enriched membrane microdomains; Tetraspanins
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-06-0384

High expression of EpCAM and the tetraspanin CO-029 has been associated with colorectal cancer progression. However, opposing
results have been reported on CD44 variant isoform v6 (CD44v6) expression. We recently noted in rat gastrointestinal tumors
that EpCAM, claudin-7, CO-029, and CD44v6 were frequently coexpressed and could form a complex. This finding suggested the
possibly that the complex, rather than the individual molecules, could support tumor progression. The expression of EpCAM,
claudin-7, CO-029, and CD44v6 expression was evaluated in colorectal cancer ( n = 104), liver metastasis ( n = 66), and tumor-free colon and liver tissue. Coexpression and complex formation of the molecules was correlated with clinical
variables and apoptosis resistance. EpCAM, claudin-7, CO-029, and CD44v6 expression was up-regulated in colon cancer and liver
metastasis. Expression of the four molecules did not correlate with tumor staging and grading. However, coexpression inversely
correlated with disease-free survival. Coexpression was accompanied by complex formation and recruitment into tetraspanin-enriched
membrane microdomains (TEM). Claudin-7 contributes to complex formation inasmuch as in the absence of claudin-7, EpCAM hardly
associates with CO-029 and CD44v6 and is not recruited into TEMs. Notably, colorectal cancer lines that expressed the EpCAM/claudin-7/CO-029/CD44v6
complex displayed a higher degree of apoptosis resistance than lines devoid of any one of the four molecules. Expression of
EpCAM, claudin-7, CO-029, and CD44v6 by themselves cannot be considered as prognostic markers in colorectal cancer. However,
claudin-7–associated EpCAM is recruited into TEM and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation.
(Mol Cancer Res 2007;5(6):553–67)