Peter Gassmann, Andreas Enns, Kerstin Schlueter, Timo Korb, Hans-Ullrich Spiegel, Norbert Senninger, Joerg Haier, Molecular Biology Lab, Dept. of General Surgery, Muenster, Germany, Dept. of General Surgery, University Hospital, Muenster, Germany

BACKGROUND: Tumor cells can show different malignant properties, such as those related to their abilities to form organ-specific distant metastasis. The colonization of different target organs is a nonrandom process, and the adhesive and invasive characteristics of circulating tumor cells appear to be crucial for this process. We investigated adhesive interactions of colon carcinoma cells within the microcirculation of different organs (liver, kidney, lung) and their behavior during early steps of organ-specific metastasis in vivo. METHODS: Single cell suspensions of human colon carcinoma of low (HT-29P: n=10; CACO-2: n=10), intermediate (KM-12C: n=9) or high (HT-29LMM: n=9; KM-12L4, n=9) metastaic potential were labeled with Calcein-AM and intracardially injected into Sprague-Dawley-rats. Initial interactions between different cell lines and the microvasulature of liver, kidney or lungs were observed over 20-30 minutes in situ and semiquantitatively analysed. RESULTS: All the cell lines showed high adhesion rates within the microvessels independent of their metastatic potential in liver and lungs, but never in the renal capillaries. The diameters of the microvessels with arrested tumor cells were larger than those of the tumor cells in both organs. Circulating cells were able to easily pass the microvessels of all organs without mechanical arrest. In addition, the relative rates of cell migration of highly metastatic HT-29-LMM and KM-12L4 cells into the liver parenchyma was significantly higher than in low metastatic HT-29P or CACO-2 cells (p<0.05). CONCLUSION: Colon carcinoma cell adhesion within potential metastatic host organs appears to be mediated by specific tumor cell-host organ interactions, and mechanical cell arrest mediated by size restriction was not observed. Our results indicate significant differences of colon carcinoma cells with different metastatic phenotypes regarding their invasion of host organ microvessels during the initial steps of host organ colonization. Invasion of tumor cells into the target organ correlated with their ability to form metastases.