Gassmann et al. BMC Cancer 2010, 10:177 http://www.biomedcentral.com/1471-2407/10/177 [10]. On the other hand we found their organ specific adhesion within liver and lung [10]. In the kidneys' glom- erula, the endothelium is discontinuously perforated by fenestrae, covering 20% of the endothelial surface [50] and the underlining ECM contains fibronectin beside col- lagen IV and laminin [51]. Inhibition of fibronectin bind- ing α5β1-integrins on CHO cells critically impaired their adhesion within the kidney without affecting their adhe- sion in the lungs [52]. In contrast, CHO cells transfected with αvβ3-integrin exhibited enhanced accumulation in the liver by binding of extracellular vitronectin, while their accumulation in the lungs did not differ from their integrin αvβ3 negative parental cells [53]. In the liver the ECM is also directly accessible for circulating TCs through fenestrae of the EC covering 6-8% of the sinusoi- dal endothelial surface [54]. Fibronectin and type IV col- lagen in the space of Dissé were found mediating metastatic HT-29LMM cell arrest in the liver, while type I collagen predominantly seemed to mediate cell extrava- sation into the liver parenchyma [6,17,55]. In addition, TCs can directly adhere to small amounts of laminins via α6β1- and α6β4-integrins in the space of Dissé [17]. The in vivo microscopy technique used in this study provided quantitative information of TC arrest in the lung, but provided insufficient resolution to observe eventual morphologic changes of adhering TC or involved EC. Since the interface between capillary lumen and alveolar air is only 0.1 μm [25,54], flattening and transendothelial migration of tumor cells cannot be excluded, but extravasated tumor cells, e.g. cells in the alveolae, were not observed in formalin fixed tissue examined by confocal laser scanning microscopy. The fate of the adherent cells remains unclear in this study and may not be determined using the model and tech- nique used here, but intravascular proliferation of adher- ent HT1080 sarcoma cells was described within the pulmonary capillaries by others [8]. In earlier studies, our group [10] and others [24] could not determine a correla- tion of cell adhesion and metastatic potential but found a positive correlation of metastatic potential and tumor cell extravasation of different colon cancer cells within the liver [10]. However, transendothelial migration that would be required within the lungs may take longer time periods since endothelial retraction and proteolysis of the pulmonary basal membrane are required in the lung, but only partially or not at all in the liver. As first adhesive interactions were observed as soon as 1 minute after cell injection and cell adhesion reached high numbers at 10 minutes after tumor cell injection, this seems not only to be a highly efficient process, but also a highly organ-spe- cific step for the formation of metastatic lesions [24]. The continuous endothelium of the pulmonary capil- lary system appears to prevent direct integrin mediated adhesion of colon cancer cells to the underlining basal Page 9 of 11 membrane. Although, single spots of exposed ECM can be found in the pulmonary capillaries [46], they do not provide sufficient binding capacity for integrin mediated adhesion. This is supported by the observation of TCs 'sticking' (temporary adhesion) without establishing firm adhesions, a phenomenon known for leucocytes but not documented for TCs in the liver [23]. As a result of initial TC-EC adhesion, conformational changes such as endothelial retraction and apoptosis of EC are well docu- mented [56]. The subsequent exposure of underlining ECM components can provide additional adhesion capacity in a second step and may trigger further cell interactions. This could explain reports of increased lung metastasis of carcinoma cells after altered β1-integrin expression [57]. It would also be in line with reports of enhanced pulmonary metastasis of fibrosarcoma cells in mice after endothelial damage by bleomycin treatment that was associated with cells adhering to exposed basal membrane [58]. Conclusions In summary, this study is the first report using intravital in-situ observation of circulating colon cancer TCs within their important metastastatic target organ of the lung. Our results support the importance of organ spe- cific histological architecture for metastatic TC coloniza- tion. While integrin mediated adhesion to ECM components may contribute to the initiation of meta- static tumor cell arrest in organs with a discontinuous endothelium like the liver, in organs with a continuous endothelial lining like the lung, initial metastatic TC adhesion appears to be exclusively mediated by direct and/or indirect TC - EC interactions via glycosylated adhesion molecules, such as selectins and TF-antigens. Abbreviations TC: tumor cell; EC: endothelial cell; ECM: extracellular matrix; sLe-a: sialyl Lewis- a; sLe-x: sialyl Lewis-x; TF: Thomson-Friedenreich antigen; Competing interests The authors declare that they have no competing interests. Authors' contributions PG established the animal model, planned major parts of the study, contrib- uted to analysing the data and drafted the manuscript. MK and STM generated the substantial body of the experimental data and contributed to the analysis of the results. JH gave the idea for the in vivo model and contributed to the interpretation of the data and drafting of the manuscript. All authors read and approved the final manuscript Acknowledgements The authors thank Mrs. K. Hagen and Mrs. I. Baumeister for excellent technical assistance and W Mardin for critical review of the manuscript. J.H. was supported by, Förderprojekt IMF der Medizinischen Fakultät Münster' (HA 1 2 01 01). Author Details Department of General and Visceral Surgery; University Hospital Muenster; Muenster; Germany