Alphavbeta5-integrins mediate early steps of metastasis formation
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Alphavbeta5-integrins mediate early steps of metastasis formation. / Enns, Andreas; Korb, Timo; Schlüter, Kerstin; Gassmann, Peter; Spiegel, Hans-Ullrich; Senninger, Norbert; Mitjans, Francesc; Haier, Jörg.
In: EUR J CANCER, Vol. 41, No. 7, 05.2005, p. 1065-72.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Alphavbeta5-integrins mediate early steps of metastasis formation
AU - Enns, Andreas
AU - Korb, Timo
AU - Schlüter, Kerstin
AU - Gassmann, Peter
AU - Spiegel, Hans-Ullrich
AU - Senninger, Norbert
AU - Mitjans, Francesc
AU - Haier, Jörg
PY - 2005/5
Y1 - 2005/5
N2 - Tumour cell adhesion within the microvasculature of host organs, its stabilisation and cell invasion into the host organs, appear to be important steps in the formation of distant metastases. Intravital fluorescence-video microscopy was used to investigate the early steps in metastasis formation of colon carcinoma cells within the liver, which is the main target organ of colorectal carcinomas. The involvement of alphav-integrins was analysed in vivo using HT-29 cells after treatment with different function-blocking antibodies [pan-alphav (n=9 animals), specific alphavbeta3 (n=8 animals) and alphavbeta5 (n=8 animals)] or linear Arg-Gly-Asp (RGD)-containing peptides (RGD-peptides) (n=6 animals). Treatment with anti-alphav and anti-alphavbeta5 antibodies resulted in significantly (P<0.001) decreased tumour cell adhesion in vivo within the hepatic microvasculature. Cells treated with anti-alphavbeta3 antibodies or unspecific immunoglobulin-G (IgG) did not show significant changes in their adhesive properties. Furthermore, inhibition of cell adhesion was achieved by linear RGD-peptides in a dose-dependent manner. Relative numbers of migrated cells were not affected by any of the treatments. These results suggest that alphav-integrins, especially alphavbeta5, can influence the ability of circulating tumour cells to adhere within the hepatic microvessels. In contrast, migration of adherent cells into the liver parenchyma was not affected by alphav-integrin inhibition. Our findings support the hypothesis that specific interactions between circulating tumour cells and host organs are required for organ-specific tumour cell arrest.
AB - Tumour cell adhesion within the microvasculature of host organs, its stabilisation and cell invasion into the host organs, appear to be important steps in the formation of distant metastases. Intravital fluorescence-video microscopy was used to investigate the early steps in metastasis formation of colon carcinoma cells within the liver, which is the main target organ of colorectal carcinomas. The involvement of alphav-integrins was analysed in vivo using HT-29 cells after treatment with different function-blocking antibodies [pan-alphav (n=9 animals), specific alphavbeta3 (n=8 animals) and alphavbeta5 (n=8 animals)] or linear Arg-Gly-Asp (RGD)-containing peptides (RGD-peptides) (n=6 animals). Treatment with anti-alphav and anti-alphavbeta5 antibodies resulted in significantly (P<0.001) decreased tumour cell adhesion in vivo within the hepatic microvasculature. Cells treated with anti-alphavbeta3 antibodies or unspecific immunoglobulin-G (IgG) did not show significant changes in their adhesive properties. Furthermore, inhibition of cell adhesion was achieved by linear RGD-peptides in a dose-dependent manner. Relative numbers of migrated cells were not affected by any of the treatments. These results suggest that alphav-integrins, especially alphavbeta5, can influence the ability of circulating tumour cells to adhere within the hepatic microvessels. In contrast, migration of adherent cells into the liver parenchyma was not affected by alphav-integrin inhibition. Our findings support the hypothesis that specific interactions between circulating tumour cells and host organs are required for organ-specific tumour cell arrest.
KW - Cell Adhesion
KW - Colonic Neoplasms
KW - Enzyme-Linked Immunosorbent Assay
KW - HT29 Cells
KW - Humans
KW - Integrins
KW - Liver Neoplasms
KW - Neoplasm Invasiveness
KW - Oligopeptides
KW - Receptors, Vitronectin
U2 - 10.1016/j.ejca.2004.12.031
DO - 10.1016/j.ejca.2004.12.031
M3 - SCORING: Journal article
C2 - 15862757
VL - 41
SP - 1065
EP - 1072
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
IS - 7
ER -