BEYOND REASON
암세포 전이의 시작은 전이가능한 mestastitic seed(전이 종자)의 Intravastion(혈관침투)임.
혈관침투 기전을 알면 전이를 막는 치료 전략을 세울수 있음.
Abstract—Intravasation is a key step in cancer metastasis during which tumor cells penetrate the vessel wall and enter circu lation, thereby becoming circulating tumor cells and potential metastatic seeds. Understanding the molecular mechanisms of intravasation is critically important for the development of therapeutic strategies to prevent metastasis.
In this article, we review current data on the mechanisms of cancer cell intravasation into the blood and lymphatic vessels. The entry of mature thymocytes into the circulation and of dendritic cells into the regional lymph nodes is considered as examples of intravasation under physiologically normal conditions. Intravasation in a pathophysiological state is illustrated by the reverse transendothe lial migration of leukocytes into the bloodstream from the sites of inflammation mediated by the sphingosine 1phosphate interaction with its receptors. Intravasation involves both invasiondependent and independent mechanisms. In particular, mesenchymal and amoeboid cell invasion, as well as neoangiogenesis and vascular remodeling, are discussed to play a signif icant role in the entry of tumor cells to the circulation. Special attention is given to the contribution of macrophages to the intravasation via the CSF1/EGF (colony stimulating factor 1/epidermal growth factor) paracrine signaling pathway and the TMEM (tumor microenvironment of metastasis)mediated mechanisms. Other mechanisms including intravasation of tumor cell clusters surrounded by the vessel wall elements, cooperative intravasation (entry of noninvasive tumor cells to the circu lation following invasive tumor cells), and intravasation associated with the vasculogenic mimicry (formation of vascular chan nels by tumor cells) are also discussed. Novel intravasationspecific mechanisms that have not yet been described in the liter ature are suggested. The importance of targeted therapeutic strategies to prevent cancer intravasation is emphasized.
