Recent data indicate that
integrin and non-
integrin collagen receptors cooperate in the
fibrosis-specific microenvironment (i.e., the fibrotic niche). In certain
tumor types, DDR1 can regulate the interaction with
collagen III to regulate dormancy and
metastasis, whereas in other
tumor types, DDR1 can be shed and used to reorganize
collagen. DDR1 expressed on
tumor cells, together with DDR2 and α11β1
integrin expressed on cancer-associated fibroblasts, can increase
tumor tissue stiffness.
Integrin α1β1 and α2β1 are present on immune cells where they together with the immunosuppressive
collagen receptor LAIR-1 can mediate binding to intratumor
collagens. In summary,
collagen-binding
integrins together with DDRs, can create
fibrillar collagen niches that act as traps to hinder immune cell trafficking into the
tumor cell mass. Binding of
collagens via LAIR-1 on immune cells in turn results in CD8+T-cell exhaustion. Continued studies of these complex interactions are needed for successful new stroma-based therapeutic interventions. In the current review, we will summarize recent data on
collagen receptors with a special focus on their potential role in
tumor fibrosis and highlight their collaborative roles in
tumor fibrotic niches.