Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-metastatic actions of tamoxifen on the oestrogen receptor-(ER-) positive cell line, MCF-7 and Hs578T, which is ER-negative, were investigated by measuring changes in the tumour cell adherence to endothelium and invasion of Matrigel. The endothelial hybridoma EA.hy926 was grown to confluence on the bases of 96-well plates. Either tamoxifen, the pure ER antagonist ICI 182,780 or the control, phosphate-buffered saline (PBS), was added to each well in varying concentrations. Adhesion of tumour cells to the endothelium was then measured using an isotopic adhesion assay. Invasion was determined by measuring the number of cells passing across a Matrigel-coated filter with 8 microm diameter pores. After 24-h incubation, the number of cells which had invaded was determined by an XTT colorimetric assay. Tamoxifen and ICI 182,780 inhibited both adhesion to the model endothelium and Matrigel invasion of the ER-positive cell line at therapeutic concentrations (P<0.005). Neither compound, however, had an effect on the ER-negative cell line. This action of the ER antagonists may play a role in prolonging the disease-free survival seen in women with breast cancer who are treated with adjuvant tamoxifen.
 ...
PMID:Inhibition of endothelial adhesion and invasion by breast carcinoma cells may contribute towards the anti-metastatic effects of tamoxifen. 884 62

Estrogen receptor (ER) plays an important role in various physiological functions. We examined whether ERalpha and ERbeta are expressed in squamous cell carcinoma (SCC), and whether ER is a potential target for antitumor therapy. High-level expression of ERbeta, but not ERalpha, was observed in tumor cells of human primary SCC tissues and various SCC cultured cell lines. Treatment with ER antagonist (tamoxifen), but not agonist (estradiol), caused apoptotic cell death of SCC cells in a concentration- and time-dependent manner. Adhesion of SCC was inhibited by the treatment with tamoxifen, but not with estradiol. Tamoxifen reduced the phosphorylation of focal adhesion kinase (FAK), resulting in decreases in phosphorylation of extracellular signal-related kinase (Erk) and mitogen-activated protein kinase. Inhibition of FAK phosphorylation is accompanied by disorder of the cytoskeletal component actin. The cell death caused by tamoxifen is therefore the result of direct interference in cell adhesion, which is called 'anoikis', involving a decrease in intracellular FAK signaling. Expression of epidermal growth factor receptor was also inhibited by treatment with a high concentration of tamoxifen. Knockdown of ERbeta by small interfering RNA inhibited the proliferation of SCC. In addition, tamoxifen strongly inhibited invasion of SCC. These results imply a potentially important role for ER, whose inhibition may be effective for the treatment of SCC and the prevention of invasion and metastasis.
 ...
PMID:Critical role of estrogen receptor on anoikis and invasion of squamous cell carcinoma. 1735 62