Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Semin Cancer Biol. 2011 Apr;21(2):99-106. doi: 10.1016/j.semcancer.2010.12.003. Epub 2010 Dec 9.
Disseminated tumor cells must negotiate multiple situations that challenge their viability and/or proliferative capacity before they can successfully colonize distant organ sites. Thus, the shear stress caused by the blood flow may physically damage tumor cells during their translocation from primary tumors to distant organs via the circulation. In addition, the tissue microenvironment of distant organs is generally unfamiliar to tumor cells, limiting their proliferation within the parenchyma of these organs. Each of these situations involves various types of interactions between tumor cells and host components, which either support or inhibit the establishment and subsequent progression of metastases. The initial formation of micrometastases, as well as their subsequent growth--often termed colonization--therefore require complex adaptations by tumor cells to various host components, most of which are never encountered by these cells during their growth within primary tumor sites. These difficulties explain why the colonization of distant organs by disseminated tumor cells is an extraordinarily demanding task and thus inefficient, and suggests a number of potential targets that might be used in the future to interfere therapeutically with this process. Studying the details of tumor-host interactions at each of the steps leading up to successful metastatic colonization may therefore pave the way for designing therapeutic strategies to counteract the metastatic spread of malignant tumors.
转移瘤细胞必须在成功定植于远处器官之前，应对多种挑战其生存力和/或增殖能力的情况。因此，在转移瘤细胞通过循环从原发肿瘤转移到远处器官的过程中，血流产生的切应力可能会对其造成物理损伤。此外，远处器官的组织微环境通常对肿瘤细胞来说是陌生的，限制了它们在这些器官实质内的增殖。这些情况中的每一种都涉及肿瘤细胞与宿主成分之间的各种类型的相互作用，这些相互作用要么支持、要么抑制转移的建立和随后的进展。微转移的最初形成，以及随后的生长——通常称为定植——因此需要肿瘤细胞对各种宿主成分进行复杂的适应，这些成分在肿瘤细胞在原发肿瘤部位生长过程中从未遇到过。这些困难解释了为什么播散性肿瘤细胞对远处器官的定植是一项极其苛刻的任务，因此效率低下，并提示了一些可能在未来用于治疗干预该过程的潜在靶点。因此，研究导致成功转移定植的每一步中肿瘤-宿主相互作用的细节，可能为设计治疗策略以对抗恶性肿瘤的转移扩散铺平道路。
