Patient-derived xenograft (PDX)
tumor models have emerged as a new approach to evaluate the effects of
cancer drugs on patients' personalized
tumor grafts enabling to select the best treatment for the
cancer patient and providing a new tool for oncology
drug developers. Here, we report that human
tumors engrafted in immunodeficient mice are susceptible to formation of B-and T-cell PDX
tumors. We xenografted human primary and metastatic
tumor samples into immunodeficient mice and found that a fraction of PDX
tumors generated from patients' samples of breast, colon, pancreatic, bladder and
renal cancer were histologically similar to lymphocytic
neoplasms. Moreover, we found that the first passage of breast and
pancreatic cancer PDX
tumors after initial
transplantation of the
tumor pieces from the same human
tumor graft could grow as a lymphocytic
tumor in one mouse and as an
adenocarcinoma in another mouse. Whereas subcutaneous PDX
tumors resembling human
adenocarcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphocytic
tumors were fast growing and formed large metastatic lesions in mouse lymph nodes, liver, lungs, and spleen. PDX lymphocytic
tumors were comprised of B-cells which were Epstein-Barr virus positive and expressed CD45 and CD20. Because B-cells are typically present in malignant solid
tumors, formation of B-cell
tumor may evolve in a wide range of PDX
tumor models. Although PDX
tumor models show great promise in the development of personalized
therapy for
cancer patients, our results suggest that confidence in any given PDX
tumor model requires careful screening of lymphocytic markers.