These findings exclude a requirement for de novo angiogenesis prior to microcolony formation. They also contrast with the classical seed and soil hypothesis for brain metastasis suggesting a neural substrate and Albaspidin-AA reliance upon neural-derived trophic factors for growth. Importantly, they do not exclude vascular remodeling or contributions from the neural elements for later growth. This work thus describes in detail a major mechanism of brain metastasis formation in addition to identifying the mechanism of vessel cooption in the brain for the first time. The CNS parenchyma is largely devoid of non-vascular stromal basement membrane components which are necessary for Chlorhexidine hydrochloride epithelial and carcinoma cell adhesion and survival. Vascular cooption, therefore, supplies substrates for malignant growth of non-neural carcinoma cells not otherwise widely available in the neuropil. Proliferation by metastatic tumor cells is highly potentiated upon adhesion to a basement membrane substratum and is attenuated by inhibiting MEK in vitro. Consistent with the experiments in tissue culture, during the early stages of colony formation in vivo we found the vast majority of micrometastases to be in direct contact with the VBM of existing brain vessels and many of these cells were proliferating. Resident neural stem cells tend to localize in perivascular locations and cells defined as brain tumor stem cells are found in a similar location. Secreted paracrine growth factors from the endothelial cells of the “perivascular niche” were shown to stimulate the growth and survival of BTSCs. In contrast, we demonstrated that slide-mounted brain sections still supplied the components needed for adhesion and spreading by carcinoma cells. The requirement of metastatic carcinoma cells for the vasculature in adhesion and invasion during metastasis in the brain may be more 
analogous to the requirement for VBM during development of pancreatic islets. Islet cells use b1 integrins to interface with the VBM and this interaction is required for proliferation and endocrine function. Nikolova et al. termed this basement membrane microenvironment, a “vascular niche”. Similarly vascular mural cells require the b1 integrin subunit for proper adhesion to vessels and for maintaining vessel stability. In an analogous fashion, carcinoma cells, then, appear to hijack the brain’s VBM for essential functions during brain metastasis.