Microenvironment in metastasis: roadblocks and supportive niches

In many cancers, malignant cells can spread from the primary tumor through blood circulation and initiate metastasis in secondary organs. Metastatic colonization may depend not only on inherent properties of cancer cells, but also on suitable microenvironments in distant sites. Increasing evidence suggests that the nature of the microenvironment may determine the fate of disseminated cancer cells, providing either hindrance or support for cancer cell propagation. This can result in strong selective pressure where the vast majority of cancer cells, invading a secondary organ, are either eliminated or maintained in a dormant state. The ability of cancer cells to fend off or circumvent anti-metastatic signals from the stroma and the capacity to manipulate the local microenvironment towards a supporting environment, a metastatic niche, may be essential for metastatic growth. The molecular interactions between cancer cells and the stroma are still enigmatic, but recent studies are beginning to reveal their nature. Here, we discuss the interactive relationship between metastatic cancer cells and host stroma, involving selection and adaptation of metastasis-initiating cells and host tissue remodeling. Understanding the dynamic and continuously evolving cross talk between metastatic cancer cells and the stroma may be crucial when developing cancer treatments.