Molecular mechanisms of cancer cell-cell interactions

This issue focuses on the molecular mechanisms by which cell-cell interactions in the tumor microenvironment lead to phenotypic changes that result in cancer progression including alterations in cell lineage, migration, invasion and metastasis. Tumors are heterotypic collections of many cell types including cancer stem cells, progeny tumor cells, stromal cells, and inflammatory cells all of which can communicate with one another via adhesive cell-cell contacts within the tumor microenvironment. Cancer stem cells interact with other cells in the tumor microenvironment to generate signals via cell adhesion molecules (CAMs) that control both cell survival and lineage. For example, cancer stem cells generate progeny tumor cells with different repertoires of cell-cell adhesion molecules allowing for distinct cell-cell interactions. In some cases this results in the generation of progeny tumor cells that are highly migratory, partly due to the specific array of cell-cell CAMs that they express. In addition, epithelial to mesenchymal transition (EMT), which occurs as some cells become tumorigenic, takes place in response to changes in adhesion molecule expression and stability. EMT is proposed to promote a migratory switch in previously adherent epithelial cells to generate motile and invasive mesenchymal-like tumor cells. Finally, changes in cell-cell CAM function also lead to a mesenchymal to epithelial (MET) lineage conversion in which a migratory cell switches to an adherent cell capable of colonizing metastases via cell-cell interactions. Together, cell-cell CAMs regulate the ability of a multiplicity of cell types to establish the unique niche called the tumor microenvironment to promote cancer progression.