Influence of phosphotyrosine kinase inhibitors on adhesive properties of highly and poorly metastatic HT-29 colon carcinoma cells to collagen
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Influence of phosphotyrosine kinase inhibitors on adhesive properties of highly and poorly metastatic HT-29 colon carcinoma cells to collagen. / Haier, J; Nasralla, M; Nicolson, G L.
in: INT J COLORECTAL DIS, Jahrgang 14, Nr. 2, 04.1999, S. 119-27.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Influence of phosphotyrosine kinase inhibitors on adhesive properties of highly and poorly metastatic HT-29 colon carcinoma cells to collagen
AU - Haier, J
AU - Nasralla, M
AU - Nicolson, G L
PY - 1999/4
Y1 - 1999/4
N2 - Organ-specific sites of metastastic lesions are determined in part by integrin-mediated adhesion to extracellular matrix (ECM) components. Using poorly (HT-29P) and highly liver-metastatic (HT-29LMM) colon carcinoma cells we previously found different integrin-mediated adhesion to various ECM components, but similar integrin expression of both cell lines. These HT-29 cell lines were used to study adhesion to collagen I (C I) and possible intracellular signaling mechanisms that could explain different adhesive properties. HT-29LMM cells had significantly poorer rates of adhesion to C I (P < 0.05) than HT-29P cells. For examination of the integrin subunits involved in adhesion to C I, cells were treated with various anti-integrin antibodies. These results demonstrated that adhesion of HT-29 cells to C I is mediated in part by the alpha 2 beta 1 integrin. Using immunoprecipitation and Western blotting, both cell lines expressed similar patterns of integrins (alpha 2, alpha 3, alpha 6, and beta 1). Weaker signals were found for the expression of alpha v and beta 5 integrins. Although poorly and highly metastatic cells possessed different patterns of adhesion to C I, these differences were not caused by different expression of integrin subunits. For investigation of the involvement of phosphotyrosine kinases in adhesion, cells were pretreated with the Erbstatin analog, Genistein, or Herbimycin A. Genistein transiently stimulated the adhesive properties of both cell lines. In contrast, Herbimycin A had biphasic effects. At lower concentrations of Herbimycin A stimulation of adhesion was found after 30 and 90 min. However, higher concentrations inhibited adhesive properties. The stimulatory effect was more pronounced in poorly metastatic HT-29P cells. The Erbstatin analog had no effect, probably because of the lack of epidermal growth factor receptor expression in both cell lines. The results suggest that adhesion of tumor cells to ECM components may be dependent on signal transduction into the cell, and tyrosine phosphorylation appears to be involved.
AB - Organ-specific sites of metastastic lesions are determined in part by integrin-mediated adhesion to extracellular matrix (ECM) components. Using poorly (HT-29P) and highly liver-metastatic (HT-29LMM) colon carcinoma cells we previously found different integrin-mediated adhesion to various ECM components, but similar integrin expression of both cell lines. These HT-29 cell lines were used to study adhesion to collagen I (C I) and possible intracellular signaling mechanisms that could explain different adhesive properties. HT-29LMM cells had significantly poorer rates of adhesion to C I (P < 0.05) than HT-29P cells. For examination of the integrin subunits involved in adhesion to C I, cells were treated with various anti-integrin antibodies. These results demonstrated that adhesion of HT-29 cells to C I is mediated in part by the alpha 2 beta 1 integrin. Using immunoprecipitation and Western blotting, both cell lines expressed similar patterns of integrins (alpha 2, alpha 3, alpha 6, and beta 1). Weaker signals were found for the expression of alpha v and beta 5 integrins. Although poorly and highly metastatic cells possessed different patterns of adhesion to C I, these differences were not caused by different expression of integrin subunits. For investigation of the involvement of phosphotyrosine kinases in adhesion, cells were pretreated with the Erbstatin analog, Genistein, or Herbimycin A. Genistein transiently stimulated the adhesive properties of both cell lines. In contrast, Herbimycin A had biphasic effects. At lower concentrations of Herbimycin A stimulation of adhesion was found after 30 and 90 min. However, higher concentrations inhibited adhesive properties. The stimulatory effect was more pronounced in poorly metastatic HT-29P cells. The Erbstatin analog had no effect, probably because of the lack of epidermal growth factor receptor expression in both cell lines. The results suggest that adhesion of tumor cells to ECM components may be dependent on signal transduction into the cell, and tyrosine phosphorylation appears to be involved.
KW - Benzoquinones
KW - Cell Adhesion
KW - Collagen
KW - Genistein
KW - HT29 Cells
KW - Humans
KW - Integrins
KW - Lactams, Macrocyclic
KW - Neoplasms
KW - Phosphorylation
KW - Protein-Tyrosine Kinases
KW - Quinones
KW - Receptors, Vitronectin
KW - Rifabutin
KW - Tyrosine
M3 - SCORING: Journal article
C2 - 10367258
VL - 14
SP - 119
EP - 127
JO - INT J COLORECTAL DIS
JF - INT J COLORECTAL DIS
SN - 0179-1958
IS - 2
ER -