Figure 3. Integrins in the host response to cancer.

Integrins expressed in many tumour-associated cell types have crucial roles in increasing tumour progression and metastasis. In endothelial cells, integrins regulate the migration, proliferation and survival necessary for angiogenesis (step 1). The interaction between pericytes and endothelial cells is crucial for the stabilization of newly formed vessels during angiogenesis. Binding of integrin α4β1 on endothelial cells to vascular cell adhesion molecule 1 (VCAM1) on pericytes plays an important part in pericyte recruitment to the neovasculature (step 2). Myeloid cells and monocytes in primary tumours contribute to disease progression by secreting cytokines and growth factors (GFs) that initiate angiogenesis and tumour cell migration (step 3). Several studies have shown that integrins have an essential role in the homing of myeloid cells and monocytes to tumours. Fibroblast infiltration into the primary tumour, known as desmoplasia, also contributes to tumour progression through increased growth factor secretion (step 4). In addition, the invading fibroblasts deposit large amounts of collagen that might result in resistance to therapy in some tumours (step 5). A recent study showed that integrins, such as α11β1, are crucial regulators of growth factor secretion by these fibroblasts. Platelet expression of αIIbβ3 may be important for interacting with tumour cells through a fibrinogen bridge, possibly aiding in metastatic dissemination (step 6).