Metastasis is the spread of tumor cells from a primary site to a secondary site within the host’s body. It is initiated by the detachment of the tumor cells from the primary tumor followed by invasion into the surrounding tissue. Thereafter the cells migrate across the endothelium and into the blood vessels (intravasation). During the intravasation the cells have to survive the sheer forces and the immune response. Upon arrival to the target organ, the cells leave the circulation and cross the endothelium to reach the host organ. Once there, the tumor cells are greeted with the organ’s local immune cells and with a hostile or inappropriate environment, where they finally have to form proliferating colonies. Metastasis is therefore far from being a straight-forward or efficient process with less than 0.1% of disseminating tumor cells (around 1 × 109 cells per day for a 1 cm size tumor) succeeding in colonizing distal organs. The identification of the involved marker during the early metastasis process will be essential for establishment of new diagnostics tools, as well as development of novel treatment strategies.
Part of the book: Cancer Metastasis
With estimated 700,000 deaths each year, colorectal carcinoma (CRC) continues to be the fourth leading cause of cancer-related deaths worldwide. Fortunately, the mortality of CRC is considered to be most avertable; hence, it is essential to develop new approaches for more accurate and early diagnosis of primary as well as metastatic CRC, including genetic and biomarker tests. In this regard, the intercellular junctions and the insulin-like growth factor (IGF) axis attract increasing attention, since they are involved in several stages of cancer and for their vital role in regulating cell survival and growth; furthermore, constituents of intercellular junctions and of the IGF axis could be used as tumor and/or metastasis markers, which are becoming the focus of increasing research activities. Our experimental results highlight the importance of gene expression changes in the tight junction proteins claudins, and in the IGF-binding proteins IGFBP3 and IGFBP7. They show additionally that claudins and IGFBPs cannot be simply defined in terms of favoring or antagonizing cancer progression but have additional properties and activities, which become apparent only in the context of liver colonization. Furthermore, their intensive modulation during the initial phase of liver colonization may suggest them as early metastasis-related markers.
Part of the book: Advances in the Molecular Understanding of Colorectal Cancer