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Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic β tumor cells

Abstract

As in the development of many human cancers, in a transgenic mouse model of β-cell carcinogenesis (Rip1Tag2), expression of neural cell adhesion molecule (NCAM) changes from the 120-kDa isoform in normal tissue to the 140/180-kDa isoforms in tumors. NCAM-deficient Rip1Tag2 mice, generated by crossing Rip1Tag2 mice with NCAM knockout mice, develop metastases, a tumor stage that is not seen in normal Rip1Tag2 mice. In contrast, overexpression of NCAM 120 in NCAM-deficient Rip1Tag2 mice prevents tumor metastasis. The results indicate that the loss of NCAM-mediated cell adhesion is one rate-limiting step in the actual metastatic dissemination of β tumor cells.

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Figure 1: NCAM expression in the stages of Rip1Tag2 tumor progression.
Figure 2: Reduced NCAM dosage results in tumor metastasis.
Figure 3: Expression of epithelial markers in β-cell metastasis.
Figure 4: Additional downregulation of NCAM expression during β-cell tumorigenesis.

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Acknowledgements

We thank A. Compagni and M. Herzig for discussions and technical support, W. Jochum for expertise in histopathology, and M. Takeichi, E. Bock, T. Jessell and D. Bitter-Suermann for antibodies. We are grateful to E. Wagner, K. Wilgenbus, M. Busslinger, and M. Cotten for critical comments on the manuscript, and H. Tkadletz for artwork. Animal care was in accordance with institutional guidelines. This work was supported in part by the Austrian Industrial Research Promotion Fund (A.-K.P., P.W. and G.C.) and by the Swedish Cancer Society, Lion's Cancer Research Foundation, Umeå University, and M. Bergvalls Stiftelse (U.D. and H.S.)

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Correspondence to Gerhard Christofori.

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Perl, AK., Dahl, U., Wilgenbus, P. et al. Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic β tumor cells. Nat Med 5, 286–291 (1999). https://doi.org/10.1038/6502

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