Metastasis, a process that requires tumor cell dissemination followed by tumor growth, is the primary cause of death in cancer patients. An essential step of tumor cell dissemination is intravasation, a process by which tumor cells cross the blood vessel endothelium and disseminate to distant sites. Studying this process is of utmost importance given that intravasation in the primary tumor, as well as the secondary and tertiary metastases, is the key step in the systemic spread of tumor cells, and that this process continues even after removal of the primary tumor. High-resolution intravital imaging of the tumor microenvironment of breast carcinoma has revealed that tumor cell intravasation exclusively occurs at doorways, termed “Tumor MicroEnvironment of Metastasis” (TMEM), composed of three different cell types: a Tie2^high/VEGF^high perivascular macrophage, a Mena overexpressing tumor cell, and an endothelial cell, all in direct contact. In this review article, we discuss the interactions between these cell types, the subsequent signaling events which lead to tumor cell intravasation, and the role of invadopodia in supporting tumor cell invasion and dissemination. We end our review by discussing how the knowledge acquired from the use of intravital imaging is now leading to new clinical trials targeting tumor cell dissemination and preventing metastatic progression.

转移是一个需要肿瘤细胞扩散然后肿瘤生长的过程，是癌症患者死亡的主要原因。肿瘤细胞传播的一个重要步骤是血管内渗入，这是肿瘤细胞穿过血管内皮并传播到远处部位的过程。鉴于原发肿瘤的血管内渗入以及继发性和三级转移是肿瘤细胞全身扩散的关键步骤，并且即使在切除原发肿瘤后，这一过程仍在继续，因此研究这一过程至关重要。乳腺癌肿瘤微环境的高分辨率活体成像显示，肿瘤细胞内渗仅发生在门口，称为“转移的肿瘤微环境”（TMEM），由三种不同的细胞类型组成：Tie2^高/VEGF^高血管周围巨噬细胞、Mena 过表达肿瘤细胞和内皮细胞，所有这些都直接接触。在这篇综述文章中，我们讨论了这些细胞类型之间的相互作用、导致肿瘤细胞内渗的后续信号事件，以及侵袭伪足在支持肿瘤细胞侵袭和传播中的作用。我们通过讨论从使用活体成像获得的知识现在如何导致针对肿瘤细胞传播和防止转移进展的新临床试验来结束我们的审查。