Cancer Research Program, McGill University Health Centre-Research Institute, 1001 Decarie Boulevard, Montreal, Quebec, H4A 3J1, Canada.
Department of Pathology, McGill University Health Centre-Research Institute, 1001 Decarie Boulevard, Montreal, Quebec, H4A 3J1, Canada.
Sci Rep. 2019 Feb 20;9(1):2384. doi: 10.1038/s41598-019-38736-y.
We reported on the ability of immortalized or oncosuppressor-mutated cells (OMCs) to uptake circulating cancer-factors and give tumors when transplanted into mice. This led to the first biological based liquid biopsy test, which we called MATER-D platform. In the present study, we showed for the first time that a different type of OMCs (PTEN-deficient human epithelial MCF10A cells) turn malignant when exposed to cancer patient's sera, confirming the concept that different cells with diverse oncosuppressor mutations can uptake cancer factors and be used in biological based liquid biopsy tests. Our observations were confirmed in a large variety of solid and haematological malignancies. This test was able to detect dysplasia and carcinomas in situ lesions in different organs and circulating factors in cancer patients years after the removal of their lesions. To our knowledge, this ability is unique and not shared by other liquid biopsy platforms. Immunohistochemistry analysis of the xenotransplants revealed identical patterns of differentiation regardless of the cancer type, showing that differentiation through horizontal transfer might be dependent on the nature of the target cells rather than the type of cancer factors. These data strengthen the notion that OMC-based liquid biopsy tests might be promising platforms for cancer screening.
我们曾报道过永生或抑癌基因突变细胞（OMCs）摄取循环肿瘤因子并在移植入小鼠后引发肿瘤的能力。这导致了首个基于生物学的液体活检测试，我们称之为 MATER-D 平台。在本研究中，我们首次表明，当暴露于癌症患者的血清时，另一种类型的 OMC（PTEN 缺失的人上皮 MCF10A 细胞）会发生恶性转化，证实了不同的具有不同抑癌基因突变的细胞可以摄取肿瘤因子并用于基于生物学的液体活检测试的概念。我们的观察结果在各种实体瘤和血液恶性肿瘤中得到了证实。该测试能够在癌症患者的病变切除多年后，检测到不同器官中的发育不良和原位癌病变以及循环因子。据我们所知，这种能力是独特的，其他液体活检平台没有共享。异种移植的免疫组织化学分析显示出无论癌症类型如何都相同的分化模式，表明通过水平转移的分化可能取决于靶细胞的性质而不是癌症因子的类型。这些数据加强了这样一种观点，即基于 OMC 的液体活检测试可能是癌症筛查的有前途的平台。
