Does integrin-mediated cell death confer tissue tropism in metastasis?

To develop metastatic capability, tumor cells must evolve the capacity to survive in novel microenvironments. Recently, we showed that metastasis of neuroblastoma cells is enhanced by loss of caspase-8, an event that occurs frequently in this malignancy. In poorly metastatic cells, unligated integrins were found to trigger activation of caspase-8, providing a selective pressure to promote its attenuation and thereby increased survival in foreign adhesive environments. Our findings suggest one mechanism by which the organotropism of metastatic cancer cells can arise.