Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology.
Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
Adv Anat Pathol. 2019 Jan;26(1):69-74. doi: 10.1097/PAP.0000000000000219.
The concept that the pattern of metastatic spread of cancer is not random and that cancer cells exhibit preferences when metastasizing to organs, dates back to 1889 when Steven Paget published his "seed and soil" hypothesis. He proposed that the spread of tumor cells is governed by interaction and cooperation between the cancer cells (seed) and the host organ (soil). Extensive studies during the last several decades have provided a better understanding of the process of metastatic spread of cancer and several stages such as intravasation, extravasation, tumor latency, and development of micrometastasis and macrometastasis have been defined. Furthermore, recent studies have shown that the target organs may be prepared for metastatic deposits by the development of premetastatic niches. This specialized microenvironment is involved in promoting tumor cell homing, colonization, and subsequent growth at the target organ. The premetastatic niche consists of accumulation of aberrant immune cells and extracellular matrix proteins in target organs. The primary tumor plays a key role in the development of premetastatic niches by producing tumor-derived soluble factors which mobilize bone marrow-derived hematopoietic cells to the premetastatic niche. Exosomes-derived from the primary tumor also contribute to cancer-favorable microenvironment in the premetastatic niches. These changes prime the initially healthy organ microenvironment and render it amenable for subsequent metastatic cell colonization.
癌症转移模式并非随机这一概念，以及癌细胞在转移到器官时具有偏好性，可以追溯到 1889 年，当时 Steven Paget 发表了他的“种子与土壤”假说。他提出，肿瘤细胞的扩散受癌细胞（种子）与宿主器官（土壤）之间的相互作用和合作所支配。在过去几十年中进行的广泛研究使人们对癌症转移扩散的过程有了更好的理解，并定义了几个阶段，如浸润、逸出、肿瘤潜伏期以及微转移和大转移的发展。此外，最近的研究表明，靶器官可能通过前转移龛的形成来为转移性沉积物做准备。这种专门的微环境参与促进肿瘤细胞归巢、定植和随后在靶器官的生长。前转移龛由靶器官中异常免疫细胞和细胞外基质蛋白的积累组成。原发肿瘤通过产生动员骨髓来源造血细胞到前转移龛的肿瘤衍生可溶性因子，在前转移龛的形成中起着关键作用。原发肿瘤衍生的外泌体也有助于前转移龛中有利于癌症的微环境。这些变化使最初健康的器官微环境变得适宜随后的转移性细胞定植。
