In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell--endothelial cell interaction
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In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell--endothelial cell interaction. / Gassmann, Peter; Kang, Mi-Li; Mees, Soeren T; Haier, Joerg.
In: BMC CANCER, Vol. 10, 2010, p. 177.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell--endothelial cell interaction
AU - Gassmann, Peter
AU - Kang, Mi-Li
AU - Mees, Soeren T
AU - Haier, Joerg
PY - 2010
Y1 - 2010
N2 - 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 beta1-, beta4-, and alphav-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.
AB - 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 beta1-, beta4-, and alphav-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.
KW - Animals
KW - Antigens, Tumor-Associated, Carbohydrate
KW - Capillaries
KW - Cell Adhesion
KW - Cell Adhesion Molecules
KW - Cell Line, Tumor
KW - Colonic Neoplasms
KW - Endothelial Cells
KW - Galectin 3
KW - Humans
KW - Integrins
KW - Lewis Blood-Group System
KW - Lung
KW - Lung Neoplasms
KW - Male
KW - Microscopy, Fluorescence
KW - Neoplastic Cells, Circulating
KW - Perfusion
KW - Rats
KW - Rats, Sprague-Dawley
KW - Respiration, Artificial
KW - Time Factors
U2 - 10.1186/1471-2407-10-177
DO - 10.1186/1471-2407-10-177
M3 - SCORING: Journal article
C2 - 20433713
VL - 10
SP - 177
JO - BMC CANCER
JF - BMC CANCER
SN - 1471-2407
ER -
