Truncation of activated leukocyte cell adhesion molecule: A gateway to melanoma metastasis

Van Kempen, L. C. L. T., Meier, F., Egeblad, M., Kersten-Niessen, M. J. F., Garbe, C., Weidle, U. H., Van Muijen, G. N. P., Herlyn, M., Bloemers, H. P. J., Swart, G. W. M. (2004) Truncation of activated leukocyte cell adhesion molecule: A gateway to melanoma metastasis. Journal of Investigative Dermatology, 122 (5). pp. 1293-1301. ISSN 0022202X (ISSN)

DOI: 10.1111/j.0022-202X.2004.22531.x


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 (ΔN-ALCAM) into metastatic cells diminished cell clustering mediated by wild-type ALCAM. We have addressed the biological effects of ΔN-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.

Item Type: Paper
Uncontrolled Keywords: ALCAM CD166 Cell motility Melanoma metastasis Proteolytic mimicry Reconstructed skin activated leukocyte cell adhesion molecule animal experiment animal model animal tissue article cancer invasion carcinogenicity cell adhesion controlled study female genetic transfection human human cell human tissue in vitro study lung metastasis melanoma mouse nonhuman priority journal protein degradation skin culture subcutaneous tissue tumor tumor growth Activated-Leukocyte Cell Adhesion Molecule Animals Cell Line, Tumor Humans Lung Neoplasms Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Skin Neoplasms Transfection Transplantation, Heterologous
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > cancer types > melanomas
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Egeblad lab
Depositing User: Matt Covey
Date: 2004
Date Deposited: 14 Mar 2013 19:51
Last Modified: 14 Mar 2013 19:51
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