Patient-derived tumor grafts authentically reflect tumor pathology, growth, metastasis, and disease outcomes (expression). Homo sapiens

Development and pre-clinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis, in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts represent the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for newly diagnosed women; orthotopic breast tumor grafting marks a step toward individualized models for tumor growth, metastasis, and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer. Overall design: Single replicates of total RNA from 12 human breast cancer tumors and xenografts of those tumors in immunodeficient mice were hybridized to Agilent Whole Human Genome expression arrays.

新型癌症疗法的开发与临床前测试，常受限于能够真实复刻肿瘤生长与转移进程的活体（in vivo）模型的匮乏。本研究报道了一种新型乳腺肿瘤生长与转移模型，其构建形式为直接取自接受乳腺癌治疗的患者的可移植肿瘤组织。该类肿瘤移植物（tumor grafts）涵盖了人类乳腺癌的异质性，并完整保留了原发肿瘤的核心特征，包括特异性位点转移能力。原代人源间充质干细胞（primary human mesenchymal stem cells）的共移植，可维持移植物的表型稳定性，并通过促进血管生成加速肿瘤生长。本研究同时证实，肿瘤移植成功率可作为新确诊女性患者疾病转归的预后标志物；原位乳腺肿瘤移植模型的建立，为构建用于肿瘤生长、转移及预后研究的个体化模型迈出了关键一步。该肿瘤移植物库同时可作为公开共享的研究资源，用于开展乳腺癌生物学相关的新型模型研究。整体实验设计：将12例人类乳腺癌肿瘤组织及其在免疫缺陷小鼠体内构建的异种移植瘤（xenografts）的总RNA单重复样本，与安捷伦（Agilent）全人类基因组表达芯片进行杂交。