Integrity of actin fibers and microtubules influences metastatic tumor cell adhesion
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Integrity of actin fibers and microtubules influences metastatic tumor cell adhesion. / Korb, Timo; Schlüter, Kerstin; Enns, Andreas; Spiegel, Hans-Ulrich; Senninger, Norbert; Nicolson, Garth L; Haier, Jörg.
in: EXP CELL RES, Jahrgang 299, Nr. 1, 10.09.2004, S. 236-47.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Integrity of actin fibers and microtubules influences metastatic tumor cell adhesion
AU - Korb, Timo
AU - Schlüter, Kerstin
AU - Enns, Andreas
AU - Spiegel, Hans-Ulrich
AU - Senninger, Norbert
AU - Nicolson, Garth L
AU - Haier, Jörg
PY - 2004/9/10
Y1 - 2004/9/10
N2 - Tumor cell adhesion within host organ microvasculature, its stabilization and invasion into host organ parenchyma appear to be important steps during formation of distant metastasis. These interactions of circulating tumor cells with the host organs occur in the presence of fluid shear forces and soluble and cellular environmental conditions of the blood that can modulate their cellular responses and possibly their metastatic efficiency. Cytoskeletal components, such as actin filaments and microtubules, can regulate biophysical characteristics and cellular signaling of the circulating cells. Therefore, we investigated the role of these cytoskeletal structures for early steps during metastasis formation in vivo and in vitro. Using an intravital observation technique, tumor cell adhesion of colon carcinoma cells within the hepatic microcirculation of rats and their invasion into liver parenchyma was observed. Disruption of actin filaments increased cell adhesion, whereas tubulin disruption inhibited adhesive interactions in vivo. The impairment of the cytoskeleton modulated adhesion-mediated cell signaling via focal adhesion kinase (FAK) and paxillin under flow conditions in vitro. In the presence of fluid flow, focal adhesions were enlarged and hyperphosphorylated, whereas stress fibers were reduced compared to static cell adhesion. Disruption of microtubules, however, partially inhibited these effects. Combining the in vivo and in vitro results, our study suggested that changes in cell rigidity and avidity of cell adhesion molecules after disruption of cytoskeletal components appear to be more important for initial adhesive interactions in vivo than their interference with adhesion-mediated cellular signal transduction.
AB - Tumor cell adhesion within host organ microvasculature, its stabilization and invasion into host organ parenchyma appear to be important steps during formation of distant metastasis. These interactions of circulating tumor cells with the host organs occur in the presence of fluid shear forces and soluble and cellular environmental conditions of the blood that can modulate their cellular responses and possibly their metastatic efficiency. Cytoskeletal components, such as actin filaments and microtubules, can regulate biophysical characteristics and cellular signaling of the circulating cells. Therefore, we investigated the role of these cytoskeletal structures for early steps during metastasis formation in vivo and in vitro. Using an intravital observation technique, tumor cell adhesion of colon carcinoma cells within the hepatic microcirculation of rats and their invasion into liver parenchyma was observed. Disruption of actin filaments increased cell adhesion, whereas tubulin disruption inhibited adhesive interactions in vivo. The impairment of the cytoskeleton modulated adhesion-mediated cell signaling via focal adhesion kinase (FAK) and paxillin under flow conditions in vitro. In the presence of fluid flow, focal adhesions were enlarged and hyperphosphorylated, whereas stress fibers were reduced compared to static cell adhesion. Disruption of microtubules, however, partially inhibited these effects. Combining the in vivo and in vitro results, our study suggested that changes in cell rigidity and avidity of cell adhesion molecules after disruption of cytoskeletal components appear to be more important for initial adhesive interactions in vivo than their interference with adhesion-mediated cellular signal transduction.
KW - Actin Cytoskeleton
KW - Animals
KW - Cell Adhesion
KW - Cytoskeletal Proteins
KW - Focal Adhesion Kinase 1
KW - Focal Adhesion Protein-Tyrosine Kinases
KW - Humans
KW - Liver
KW - Male
KW - Microcirculation
KW - Microtubules
KW - Neoplasm Metastasis
KW - Neoplasms
KW - Paxillin
KW - Phosphoproteins
KW - Phosphorylation
KW - Protein-Tyrosine Kinases
KW - Rats
KW - Rats, Sprague-Dawley
KW - Regional Blood Flow
KW - Signal Transduction
KW - Tubulin
KW - Tubulin Modulators
KW - Tumor Cells, Cultured
U2 - 10.1016/j.yexcr.2004.06.001
DO - 10.1016/j.yexcr.2004.06.001
M3 - SCORING: Journal article
C2 - 15302590
VL - 299
SP - 236
EP - 247
JO - EXP CELL RES
JF - EXP CELL RES
SN - 0014-4827
IS - 1
ER -