Integrins can directly mediate metastatic tumor cell adhesion within the liver sinusoids
Standard
Integrins can directly mediate metastatic tumor cell adhesion within the liver sinusoids. / Enns, Andreas; Gassmann, Peter; Schlüter, Kerstin; Korb, Timo; Spiegel, Hans-Ullrich; Senninger, Norbert; Haier, Jörg.
in: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Jahrgang 8, Nr. 8, 12.2004, S. 1049-59; discussion 1060.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Integrins can directly mediate metastatic tumor cell adhesion within the liver sinusoids
AU - Enns, Andreas
AU - Gassmann, Peter
AU - Schlüter, Kerstin
AU - Korb, Timo
AU - Spiegel, Hans-Ullrich
AU - Senninger, Norbert
AU - Haier, Jörg
PY - 2004/12
Y1 - 2004/12
N2 - Tumor cells can show different malignant properties regarding their ability for organ-specific metastasis formation. Their adhesive and invasive characteristics mediated by various cell adhesion molecules appear to be crucial for this process. Using intravital fluorescence microscopy, we analyzed the adhesive and invasive interactions of circulating human colon carcinoma cells within the microvasculature of the liver in rats. The involvement of different cell adhesion molecules in specific tumor cell-host organ interactions was investigated. Single-cell suspensions of human colon carcinoma with low (HT-29P) and high (HT-29LMM) metastatic potential were fluorescence labeled with calcein-AM and intra-arterially injected into Sprague-Dawley rats. Initial interactions between different cell lines and the microvasculature of the liver were observed over 30 minutes and semiquantitatively analyzed. Different integrin subunits, carbohydrate ligands, and vascular cell adhesion molecule-1 were inhibited using function-blocking antibodies or by enzymatic removal. Inhibition of sialyl-Lewis(a) (sLe(a)) or enzymatic removal of selectin carbohydrate ligands significantly reduced metastatic cell adhesion. In addition, alpha6-, beta1-, and beta4-integrins can directly mediate cell adhesion within the hepatic microcirculation. Furthermore, alpha2-, alpha6-, beta1-, and beta4-integrins are involved in early tumor cell extravasation into the liver parenchyma. Organ-specific formation of colorectal metastases appears to be mainly mediated by specific interactions between circulating carcinoma cells and the vessel wall of target organs but not mechanical entrapment. Selectin-sLe(a) interactions with sinusoidal endothelial cells can play a key role in organ-specific targeting, but direct integrin-mediated cell adhesion to extracellular matrix components in the space of Disse appears to be required for the successful formation of liver metastases.
AB - Tumor cells can show different malignant properties regarding their ability for organ-specific metastasis formation. Their adhesive and invasive characteristics mediated by various cell adhesion molecules appear to be crucial for this process. Using intravital fluorescence microscopy, we analyzed the adhesive and invasive interactions of circulating human colon carcinoma cells within the microvasculature of the liver in rats. The involvement of different cell adhesion molecules in specific tumor cell-host organ interactions was investigated. Single-cell suspensions of human colon carcinoma with low (HT-29P) and high (HT-29LMM) metastatic potential were fluorescence labeled with calcein-AM and intra-arterially injected into Sprague-Dawley rats. Initial interactions between different cell lines and the microvasculature of the liver were observed over 30 minutes and semiquantitatively analyzed. Different integrin subunits, carbohydrate ligands, and vascular cell adhesion molecule-1 were inhibited using function-blocking antibodies or by enzymatic removal. Inhibition of sialyl-Lewis(a) (sLe(a)) or enzymatic removal of selectin carbohydrate ligands significantly reduced metastatic cell adhesion. In addition, alpha6-, beta1-, and beta4-integrins can directly mediate cell adhesion within the hepatic microcirculation. Furthermore, alpha2-, alpha6-, beta1-, and beta4-integrins are involved in early tumor cell extravasation into the liver parenchyma. Organ-specific formation of colorectal metastases appears to be mainly mediated by specific interactions between circulating carcinoma cells and the vessel wall of target organs but not mechanical entrapment. Selectin-sLe(a) interactions with sinusoidal endothelial cells can play a key role in organ-specific targeting, but direct integrin-mediated cell adhesion to extracellular matrix components in the space of Disse appears to be required for the successful formation of liver metastases.
KW - Animals
KW - Cell Adhesion
KW - Cell Adhesion Molecules
KW - Colonic Neoplasms
KW - Humans
KW - Integrin beta Chains
KW - Liver
KW - Liver Neoplasms
KW - Male
KW - Microscopy, Fluorescence
KW - Rats
KW - Rats, Sprague-Dawley
U2 - 10.1016/j.gassur.2004.08.016
DO - 10.1016/j.gassur.2004.08.016
M3 - SCORING: Journal article
C2 - 15585393
VL - 8
SP - 1049-59; discussion 1060
JO - J GASTROINTEST SURG
JF - J GASTROINTEST SURG
SN - 1091-255X
IS - 8
ER -