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 Benzoylaconine anti-b1 integrin subunit antibodies induced apoptosis in 3,4,5-Trimethoxyphenylacetic acid 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, tumors were analyzed in the MMTV/PyMT transgenic model of breast cancer. 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 transporter.