Gassmann et al. BMC Cancer 2010, 10:177 http://www.biomedcentral.com/1471-2407/10/177 R E S E A R C H A R T I C L E Open Access IRnesevarcihvaortictleumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction Peter Gassmann*, Mi-Li Kang, Soeren T Mees and Joerg Haier Abstract Background: Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer. Methods: Anaesthetized CD rats were mechanically ventilated and 106 human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection. Results: After vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against β1-, β4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p < 0.05). The same degree of impairment was achieved by inhibition of P- and L-selectins via animal treatment with fucoidan (p < 0.05) and also by inhibition of the Thomson-Friedenreich (TF)-antigen (p < 0.05). Conclusions: These results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells. Background One third of patients diagnosed with colo-rectal cancer will eventually die from this disease representing ~600,000 deaths worldwide per year [1]. Most of these colo-rectal cancer related deaths are due to distant meta- static growth rather than local tumor progression. As in almost any cancer, the pattern of metastatic growth is non-random and in the case of colo-rectal cancer liver and lung are predominant metastatic targets, beside lymph nodes and the peritoneal cavity [2]. The organ spe- cific character of metastatic growth has already been rec- * Correspondence: Peter.Gassmann@ukmuenster.de 1 Department of General and Visceral Surgery; University Hospital Muenster; Muenster; Germany Full list of author information is available at the end of the article ognised by S. Paget [3] in the late 19th century and his 'seed-and-soil concept' has been modified by additional findings and dissected into single steps, outlined in the literature as the 'metastatic cascade' [4]. Based on various in vivo and ex vivo techniques, several groups suggested mechanically restricted tumor cell embolism in the first capillary bed entered by circulating tumor cells [4,5]. In contrast, our own group [6] and other authors [7] demonstrated specific tumor cell adhe- sion in the microcirculation of the liver and lung [8,9]. Furthermore, injected human colon cancer cells showed an organ specific pattern of cell adhesion in rats, mimick- ing the clinical picture of metastatic colon cancer [10]. Glinksii et al. [11] reported organ-selective metastatic © 2010 Gassmann et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Com- BioMed Central mons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduc- tion in any medium, provided the original work is properly cited.