The neuropilin 2 isoform NRP2b uniquely supports TGFβ-mediated progression in lung cancer

Neuropilins are pleiotropic co-receptors for semaphorins and other growth factors, such as TGFβ. In established tumors, TGFβ promotes cell migration and metastasis. Using cell lines, mouse models, and primary patient material, Gemmill et al . found that the roles of the two neuropilin 2 isoforms were distinct in non–small cell lung cancer (NSCLC) cells. Experiments with cultured cells and xenografted tumors with high and low abundance of NRP2a and NRP2b showed that, in contrast to NRP2a, NRP2b inhibited primary tumor growth but mediated TGFβ-induced epithelial-to-mesenchymal transition, cell migration, metastasis, and drug resistance. High amounts of NRP2b in tumors correlated with that of the immunosuppressive ligand PD-L1 and with drug resistance, metastatic disease, and poor prognosis in patients. Selectively targeting this isoform may prevent disease progression and improve drug efficacy in some patients.