Podocalyxin (PCLP1) is a CD34-related sialomucin expressed by some normal cells and a variety of malignant tumors, including leukemia, and associated with the most aggressive cancers and poor clinical outcome. PCLP1 increases breast tumor growth, migration and invasion; however, its role in hematologic malignancies still remains undetermined. The purpose of this study was to investigate the expression and function of PCLP1 in mature B-cell lymphoma cells. We found that overexpression of PCLP1 significantly increases proliferation, cell-to-cell interaction, clonogenicity, and migration of B-cell lymphoma cells. Furthermore, PCLP1 overexpression results in higher resistance to death induced by dexamethasone, reactive oxygen species and type II anti-CD20 monoclonal antibody obinutuzumab. Strikingly, enforced expression of PCLP1 enhances lipid droplet formation as well as pentose phosphate pathway and glutamine dependence, indicative of metabolic reprogramming necessary to support the abnormal proliferation rate of tumor cells. Flow cytometry analysis revealed augmented levels of PCLP1 in malignant cells from some patients with mature B-cell lymphoma compared to their normal B-cell counterparts. In summary, our results demonstrate that PCLP1 contributes to proliferation and survival of mature B-cell lymphoma cells, suggesting that PCLP1 may promote lymphomagenesis and represents a therapeutic target for the treatment of B-cell lymphomas.
Keywords: glutaminolysis; lymphomagenesis; obinutuzumab resistance; pentose phosphate pathway; podocalyxin.