Activated leukocyte cell adhesion molecule (
ALCAM/CD166) is a progression marker of a variety of
cancers, including
melanoma, and is a marker for mesenchymal stem cells.
ALCAM expression triggers
matrix metalloproteinase activity and correlates with the transition between superficial
melanoma growth and deep dermal invasion in vivo. We previously showed that manipulating
ALCAM functionality could both decrease and increase
melanoma invasion, depending on the manner by which
ALCAM function was altered. How
ALCAM exerts these opposing invasive phenotypes remained elusive. In the present study, we analyzed differences in
melanoma cell gene expression in two- and three-dimensional cultures as function of
ALCAM-mediated adhesion. We identified a cluster of genes highly responsive to
ALCAM functionality and relevant for
melanoma invasion. This cluster is characterized by known invasion-related genes similar to L1 neuronal
cell adhesion molecule and showed a remarkable induction of several innate immune genes. Unexpectedly, we identified major variations in the expression of genes related to an immunological response when modulating
ALCAM function, including
complement factors C1r and C1s. The expression and function of these
proteinases were confirmed in
protein assays and in vivo. Together, our results demonstrate a link between
ALCAM functionality and the immune transcriptome, and support the assumption that
ALCAM-
ALCAM interactions could function as a cell signaling complex to promote
melanoma tumor invasion.