Cancer metastasis is often more deadly than the primary tumor. Wang et al. report on page 935 that exposed basement membrane may offer a docking site when tumors spread to the lung—the most common site of metastasis.
Some existing metastasis studies have used long time points that may mask several sequential events. Wang et al. targeted the point of initial cell attachment by developing an ex vivo lung perfusion model. After injecting fluorescent tumor cells into rat renal vein, they immediately isolated the lungs allowing them to measure arrest of cells in pulmonary tissue.
Prior treatment with a range of integrin antibodies revealed that α3β1 integrin—which is widely expressed in cancerous cells—is the key player in tumor cell attachment. This was confirmed by genetic deletion and restoration of the distinct α3 and β1 subunits in a variety of cells.
Having found the anchor, the team then needed to know where it came to rest on the blood vessel wall. And here, perhaps, is the most fascinating part of their discovery: they found that the basement membrane of pulmonary vessels contains “bald patches” where laminin 5, α3β1's most common ligand, is exposed. The authors believe that many other organs don't have such patches. There is, however, exposed basement membrane in the liver, and laminins 5 and 10 are exposed in the bone marrow. Both of these are strong sites of metastasis. ▪