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Publication year
2004Source
Journal of Investigative Dermatology, 122, 5, (2004), pp. 1293-301ISSN
Publication type
Article / Letter to editor

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Organization
Pathology
Biomolecular Chemistry
Journal title
Journal of Investigative Dermatology
Volume
vol. 122
Issue
iss. 5
Page start
p. 1293
Page end
p. 301
Subject
Bio-Molecular Chemistry; UMCN 1.3: Tumor microenvironmentAbstract
Progression of human cutaneous primary melanoma is, among others, accompanied by de novo expression of activated leukocyte cell adhesion molecule (ALCAM/CD166) and enhanced activity of proteolytic cascades in the invasive, vertical growth phase (VGP) of lesions. The homophilic cell adhesion function of wild-type ALCAM mediates homotypic clustering of melanoma cells and would, thus, antagonize cell release from the primary tumor, an early prerequisite for metastasis. Stable transfection of a transmembrane, amino-terminally truncated ALCAM (DeltaN-ALCAM) into metastatic cells diminished cell clustering mediated by wild-type ALCAM. We have addressed the biological effects of DeltaN-ALCAM on tumorigenicity and found that the relief of cell clustering constraints promoted motility in vitro and the transition from expansive tumor growth to tissue invasion in reconstructed skin in culture. In a transplant tumor model, the changes were reflected in reduced subcutaneous tumor growth and in accelerated, spontaneous lung metastasis. These data indicate that the intact cell adhesion function of ALCAM may both favor primary tumor growth and represent a rate-limiting step for tissue invasion from VGP melanoma. ALCAM induction could, thus, provide an attractive target for proteolysis as a part of a more complex cellular program that couples growth and migration and facilitates dissemination.
This item appears in the following Collection(s)
- Academic publications [227902]
- Electronic publications [107427]
- Faculty of Medical Sciences [86234]
- Faculty of Science [33781]
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