Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors.
Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors.
复制标题
DOI：
10.1016/j.neo.2015.09.004
复制
发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Mazar AP
中科院分区：
文献类型：
--
作者：
Bondarenko G;Ugolkov A;Rohan S;Kulesza P;Dubrovskyi O;Gursel D;Mathews J;O'Halloran TV;Wei JJ;Mazar AP
患者衍生异种移植(PDX)肿瘤模型是评价抗癌药物对患者个体化移植瘤影响的一种新方法，能够为癌症患者选择最佳治疗方案，为肿瘤药物的研发提供了新的工具。在这里，我们报告了移植到免疫缺陷小鼠体内的人类肿瘤容易形成B细胞和T细胞PDX肿瘤。我们将人的原发和转移肿瘤样本移植到免疫缺陷小鼠中，发现从乳腺癌、结肠癌、胰腺癌、膀胱癌和肾癌患者的样本中产生的PDX肿瘤的一部分在组织学上类似于淋巴细胞性肿瘤。此外，我们发现，最初从同一人类肿瘤移植物中移植肿瘤片段后，第一代乳腺癌和胰腺癌PDX肿瘤在一只小鼠身上可以生长为淋巴细胞性肿瘤，在另一只小鼠中可以生长为腺癌。与人类腺癌组织学相似，皮下PDX肿瘤生长缓慢且无转移，而我们发现皮下PDX淋巴细胞性肿瘤生长迅速，并在小鼠的淋巴结、肝、肺和脾形成大的转移灶。PDX淋巴细胞性肿瘤由EB病毒阳性、表达CD45和CD20的B细胞组成。由于B细胞通常存在于恶性实体瘤中，B细胞肿瘤的形成可能在多种PDX肿瘤模型中演变。尽管PDX肿瘤模型在癌症患者个性化治疗的发展中显示出巨大的希望，但我们的结果表明，对任何给定的PDX肿瘤模型的信心都需要仔细筛选淋巴细胞标记物。
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.