An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation

TY - JOUR

T1 - An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation

AU - Haier, Jörg

AU - Korb, Timo

AU - Hotz, Birgit

AU - Spiegel, Hans Ullrich

AU - Senninger, Norbert

PY - 2003/5/24

Y1 - 2003/5/24

N2 - Organ-specific tumor cell adhesion within the microcirculation of host organs is an important step in the metastatic cascade. Circulating tumor cells have to adhere within the microcirculatory vessels, quickly stabilize their adhesion and probably leave the circulation to avoid toxic effects of hydrodynamic shear forces of circulating blood. Using intravital fluorescence microscopy we established a new model for the intravital observation of colon carcinoma cell adhesion within the hepatic microcirculation. HT-29 (human) and CC531 (rat) colon carcinoma cells were fluorescence labeled using CalceinAM. Single cell suspensions were injected intraarterially in Sprague-Dawley rats. Using intravital fluorescence microscopy adhesive interactions of circulating tumor cells within the hepatic microcirculation were observed at the liver surface. These interactions were analyzed regarding their time course and the localization within the vascular tree. Autofluorescence of liver parenchyma was sufficient for distinction of hepatic sinusoids. Intravital microscopy enabled the differentiation of early events in adhesion formation within hepatic sinosoids, adhesion stabilization, and extravasation of the tumor cells into the liver parenchyma. Tumor cell adhesion occurred almost exclusively within sinusoidal capillaries; however, the diameter of these vessels was usually larger than that of the tumor cells leaving remaining perfused lumen of the capillaries. Colon carcinoma cells rapidly migrated into the liver parenchyma after successful adhesion within the sinusoids. In contrast to common endpoint assays of the metastatic cascade, this in vivo model allows investigations of metastatic colon carcinoma cell adhesion within the liver microcirculation as specific steps during the formation of hematogenous metastasis and their underlying mechanisms.

AB - Organ-specific tumor cell adhesion within the microcirculation of host organs is an important step in the metastatic cascade. Circulating tumor cells have to adhere within the microcirculatory vessels, quickly stabilize their adhesion and probably leave the circulation to avoid toxic effects of hydrodynamic shear forces of circulating blood. Using intravital fluorescence microscopy we established a new model for the intravital observation of colon carcinoma cell adhesion within the hepatic microcirculation. HT-29 (human) and CC531 (rat) colon carcinoma cells were fluorescence labeled using CalceinAM. Single cell suspensions were injected intraarterially in Sprague-Dawley rats. Using intravital fluorescence microscopy adhesive interactions of circulating tumor cells within the hepatic microcirculation were observed at the liver surface. These interactions were analyzed regarding their time course and the localization within the vascular tree. Autofluorescence of liver parenchyma was sufficient for distinction of hepatic sinusoids. Intravital microscopy enabled the differentiation of early events in adhesion formation within hepatic sinosoids, adhesion stabilization, and extravasation of the tumor cells into the liver parenchyma. Tumor cell adhesion occurred almost exclusively within sinusoidal capillaries; however, the diameter of these vessels was usually larger than that of the tumor cells leaving remaining perfused lumen of the capillaries. Colon carcinoma cells rapidly migrated into the liver parenchyma after successful adhesion within the sinusoids. In contrast to common endpoint assays of the metastatic cascade, this in vivo model allows investigations of metastatic colon carcinoma cell adhesion within the liver microcirculation as specific steps during the formation of hematogenous metastasis and their underlying mechanisms.

KW - Animals

KW - Cell Adhesion

KW - Colonic Neoplasms

KW - Disease Models, Animal

KW - Fluoresceins

KW - Fluorescent Dyes

KW - Liver

KW - Liver Neoplasms

KW - Male

KW - Microcirculation

KW - Neoplasm Metastasis

KW - Neoplastic Cells, Circulating

KW - Rats

KW - Rats, Sprague-Dawley

M3 - SCORING: Journal article

C2 - 12763408

VL - 7

SP - 507-14; discussion 514-5

JO - J GASTROINTEST SURG

JF - J GASTROINTEST SURG

SN - 1091-255X

IS - 4

ER -