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 LOUREIRIN-B 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 4-(Benzyloxy)phenol brain’s VBM for essential functions during brain metastasis. Interestingly, inhibiting angiogenesis in circumscribed, well-established CNS melanoma metastases causes reversion to growth by vascular cooption. This suggests a continuum for vessel utilization by tumor cells which may represent a viable target for therapeutic exploitation. The interaction between the tumor cells and the vessels relies on b1 integrin-mediated tumor cell adhesion to the vascular basement membrane of blood vessels. This interaction is sufficient to promote immediate proliferation and micrometastasis establishment of tumor lines in the brain. This angiotropic mechanism was universal to both carcinomas and lymphomas in the CNS. b1 integrins play a dominant role in many facets of normal cell biology and have been implicated in cancer initiation, progression, and metastasis. There are at least 10 b1 integrin heterodimers which serve as variably promiscuous adhesive receptors to diverse ligands such as the collagens and laminins. Nonetheless our data suggest that antagonism of the b1 integrin subunit alone might be useful in therapeutic strategies for brain metastases. Indeed, Park et al found that inhibitory anti-b1 integrin subunit antibodies induced apoptosis in breast carcinoma cells grown in three dimensional culture, but not in cells grown in monolayers. Treating mice bearing breast cancer xenografts from those cell lines with the same antibody led to decreased tumor volume. In addition to the apoptotic mechanism described in vitro, inhibition of vascular cooption may have also attenuated growth. In an alternative strategy to evaluate the role of b1 integrins. Conditional deletion of b1 integrin after induction of tumorigenesis resulted in impairment of FAK phosphorylation and proliferation consistent with a reliance on anchorage-dependent signaling for tumor growth. Although the presence of the b1 integrin subunit is mandatory for embryonic development, chronic systemic anti-b1 antibody therapy did not result in overt toxicities in adult mice. Further research 
into the regulation of b1 integrin regulation, function and downstream signaling may yield clinically useful applications for metastatic disease in cancer patients. The quaternary structure of polytopic transmembrane proteins plays a critical role in defining their subcellular localization and, consequently, their function. For example, homo-dimerization regulates function and trafficking along the exocytic pathway of proteins as diverse as neurotransmitter transporters.