Arena Goffredo Orazio, Arena Vincenzo, Arena Manuel, Abdouh Mohamed
Cancer Research Program, McGill University Health Centre-Research Institute, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada; Department of Surgery, McGill University, St. Mary Hospital, 3830 Lacombe Avenue, Montreal, Quebec H3T 1M5, Canada.
Department of Obstetrics and Gynecology, Santo Bambino Hospital, via Torre del Vescovo 4, Catania, Italy.
Med Hypotheses. 2017 Mar;100:82-86. doi: 10.1016/j.mehy.2017.01.019. Epub 2017 Feb 1.
Metastatic disease is believed to develop following dissemination of cells to target organs. Inability of this theory to effectively explain certain phenomena such as patterns of metastatic spread, late metastasis formation, different gene patterns between primary cancer and metastasis have brought forward the need for alternative models. Recent discoveries have strengthened the validity of theories supporting a humoral transfer of malignant traits as opposed to migration of malignant cells to explain metastatic disease in cancer patients. In light of this new evidence, we would like to highlight a model that offers a new perspective to explain cancer metastasis. In the system that we theorize, genetic material released by cancer cells would travel, either free or packed in exosomes, through the blood. Target cells located in organs deriving from the same embryological layer might uptake this genetic material due to expression of specific receptors. Interplay with the immune system would determine the fate of these oncofactors and would regulate their ability to circulate in the blood, integrate in the genome and be transcribed. We also hypothesize that the expression of cell membrane receptors such as integrins, to which cancer exosomes ligate might be mediated by inherited or acquired oncosuppressor mutations.
转移性疾病被认为是在细胞扩散到靶器官后发生的。该理论无法有效解释某些现象,如转移扩散模式、晚期转移形成、原发性癌症与转移灶之间不同的基因模式,这就提出了需要替代模型的必要性。最近的发现强化了支持恶性特征体液转移而非恶性细胞迁移来解释癌症患者转移性疾病的理论的有效性。鉴于这一新证据,我们想强调一个能为解释癌症转移提供新视角的模型。在我们提出的理论体系中,癌细胞释放的遗传物质会以游离状态或包裹在外泌体中通过血液传播。位于源自同一胚胎层的器官中的靶细胞可能由于特定受体的表达而摄取这种遗传物质。与免疫系统的相互作用将决定这些致癌因子的命运,并调节它们在血液中循环、整合到基因组中并被转录的能力。我们还假设,癌症外泌体所连接的细胞膜受体如整合素的表达可能由遗传性或获得性肿瘤抑制基因突变介导。