Metastatic tumor cell arrest in the liver-lumen occlusion and specific adhesion are not exclusive
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Metastatic tumor cell arrest in the liver-lumen occlusion and specific adhesion are not exclusive. / Gassmann, Peter; Hemping-Bovenkerk, Andre; Mees, Soeren Torge; Haier, Joerg.
in: INT J COLORECTAL DIS, Jahrgang 24, Nr. 7, 07.2009, S. 851-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Metastatic tumor cell arrest in the liver-lumen occlusion and specific adhesion are not exclusive
AU - Gassmann, Peter
AU - Hemping-Bovenkerk, Andre
AU - Mees, Soeren Torge
AU - Haier, Joerg
PY - 2009/7
Y1 - 2009/7
N2 - INTRODUCTION: In metastasis research, modern microscopic techniques shed a new light on the mechanisms of metastatic tumor cell arrest in the microcirculation of potential metastasis target organs. In this study, we differentiated the contribution of mechanical cell arrest, determined as lumen occlusion of liver sinusoids by tumor cells, and specific cell adhesion mediated by integrins for the arrest of human colon cancer cells in rat livers.MATERIALS AND METHODS: Using in vivo microscopy, the diameters of liver sinusoids of two different rat strains (CD, 250-300 g and RNU, 80-120 g) were determined. Cells (HT-29LMM) were intracardially injected, and the numbers of arrested cells and the rates of sinusoid occluding cells were determined.RESULTS: Mean sinusoid diameter in CD rats was 6.98 +/- 1.42 microm compared to 5.14 +/- 1.11 microm in RNU rats (p < 0.001). The numbers of arrested tumor cells and the rates of extravasated tumor cells did not differ between the two rat strains. Nevertheless, 5 and 30 min after cell injection, 35 +/- 15% and 19 +/- 8% of arrested cells, respectively, appeared lumen occluding in RNU rats and 9 +/- 6% and 3 +/- 3%, respectively, in CD rats (p < 0.05). Despite the higher rates of lumen occlusive cells in RNU rats, inhibition of beta-1 or beta-4 integrins significantly impaired cell arrest by 30-60% in both strains.DISCUSSION: In summary, these results demonstrate that lumen occlusion alone, as determined by in vivo microscopy, is insufficient to establish stable tumor cell arrest of colon carcinoma cells in metastatic target organs and does therefore not rule out the requirement of specific adhesive interactions for tumor cell arrest in the microcirculation.
AB - INTRODUCTION: In metastasis research, modern microscopic techniques shed a new light on the mechanisms of metastatic tumor cell arrest in the microcirculation of potential metastasis target organs. In this study, we differentiated the contribution of mechanical cell arrest, determined as lumen occlusion of liver sinusoids by tumor cells, and specific cell adhesion mediated by integrins for the arrest of human colon cancer cells in rat livers.MATERIALS AND METHODS: Using in vivo microscopy, the diameters of liver sinusoids of two different rat strains (CD, 250-300 g and RNU, 80-120 g) were determined. Cells (HT-29LMM) were intracardially injected, and the numbers of arrested cells and the rates of sinusoid occluding cells were determined.RESULTS: Mean sinusoid diameter in CD rats was 6.98 +/- 1.42 microm compared to 5.14 +/- 1.11 microm in RNU rats (p < 0.001). The numbers of arrested tumor cells and the rates of extravasated tumor cells did not differ between the two rat strains. Nevertheless, 5 and 30 min after cell injection, 35 +/- 15% and 19 +/- 8% of arrested cells, respectively, appeared lumen occluding in RNU rats and 9 +/- 6% and 3 +/- 3%, respectively, in CD rats (p < 0.05). Despite the higher rates of lumen occlusive cells in RNU rats, inhibition of beta-1 or beta-4 integrins significantly impaired cell arrest by 30-60% in both strains.DISCUSSION: In summary, these results demonstrate that lumen occlusion alone, as determined by in vivo microscopy, is insufficient to establish stable tumor cell arrest of colon carcinoma cells in metastatic target organs and does therefore not rule out the requirement of specific adhesive interactions for tumor cell arrest in the microcirculation.
KW - Animals
KW - Cell Adhesion
KW - Cell Line, Tumor
KW - Colonic Neoplasms
KW - Hepatic Veno-Occlusive Disease
KW - Humans
KW - Integrins
KW - Liver
KW - Male
KW - Microscopy, Fluorescence
KW - Neoplasm Metastasis
KW - Rats
KW - Rats, Sprague-Dawley
U2 - 10.1007/s00384-009-0694-2
DO - 10.1007/s00384-009-0694-2
M3 - SCORING: Journal article
C2 - 19319542
VL - 24
SP - 851
EP - 858
JO - INT J COLORECTAL DIS
JF - INT J COLORECTAL DIS
SN - 0179-1958
IS - 7
ER -