The role of tetraspanin proteins in the regulation of the tumour microenvironment.

The immune cell landscape within tumour microenvironment is controlled by an elaborate network of communications involving chemokines, cytokines and growth factors which are produced by tumour-infiltrating immune cells themselves, by cancer cells and by other cell types in cancerous tissues (e.g. tumour endothelium, tumour-associated fibroblasts). Four transmembrane domain proteins of the tetraspanin superfamily have recently emerged as important regulators of tumour microenvironment by regulating the activity of matrix metalloproteases which facilitate release of surface-associated chemokines, cytokines and growth factors and reorganise the extracellular matrix (ECM). Tetraspanins may also act via exosomes, small secreted nanovesicles, which facilitate both short- and long-range communications between various cell types. In this regard, tetraspanins are abundant on exosomes and changes in tetraspanin expression have an impact on the protein composition of exosomes. We have demonstrated that the expression of various tetraspanin proteins is dysregulated in breast cancers and this correlated with variations in the profile of immune cells that are recruited to the cancerous tissues. Currently we are focused on identifying molecular networks underlying tetraspanin-dependent changes in the immune microenvironment in breast and colorectal cancers.