Gerard Blobe and colleagues from Duke University showed that expression of T-beta-RIII by human breast cancer samples markedly decreased or was lost with disease progression. Conversely, in a mouse model of breast cancer, tumor cells engineered to express high levels of T-beta-RIII were less able to invade the breast tissue and to metastasize to other organs than tumor cells not engineered to express this protein. Further analysis revealed that the mechanism behind these protective effects of T-beta-RIII was likely to be T-beta-RIII cleavage at the cell membrane, which releases soluble T-beta-RIII that blocks TGF-beta signaling. As low levels of T-beta-RIII were found to be associated with decreased recurrence-free survival of patients with breast cancer and loss of T-beta-RIII was found to begin before tumors became invasive, the authors suggest that analysis of T-beta-RIII levels might help clinicians decide how aggressively to treat their patients.
Source:Journal of Clinical Investigation