Tamoxifen resistance in breast cancer cells is accompanied by an enhanced motile and invasive phenotype: inhibition by gefitinib ('Iressa', ZD1839).


:Despite an initial response to antihormonal therapies, the development of resistance will occur in a significant number of breast cancer patients. The mechanisms that underlie acquired resistance are not yet clear. Using a previously established in vitro cell model of tamoxifen resistance in MCF7 cells, shown to display autocrine epidermal growth factor receptor (EGFR) signalling, we assessed how resistance might modulate their metastatic phenotype in vitro, as metastatic disease is the single most important factor affecting the mortality of cancer patients. Furthermore, we investigated the effect of the EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib ('Iressa', ZD1839; AstraZeneca), on this behaviour. The acquisition of tamoxifen resistance in MCF7 cells was accompanied by a dramatic and significant increase in their invasive and motile nature. The affinity of these cells for matrix components was also enhanced. Inhibition of EGFR signalling with gefitinib reduced both basal and TGF-alpha-stimulated invasion and motility and reduced cell-matrix adhesion. In conclusion, we demonstrate here that resistance to tamoxifen in breast cancer cells is accompanied by a significant increase in their basal motile and invasive activity, properties associated with increased metastatic potential. Inhibition of EGFR signalling by gefitinib significantly inhibited cell motility and invasion thus suggesting a role for the EGF receptor in the aggressive phenotype of tamoxifen-resistant breast cancer cells.


Clin Exp Metastasis


Hiscox S,Morgan L,Barrow D,Dutkowskil C,Wakeling A,Nicholson RI




Has Abstract


2004-01-01 00:00:00












  • Role of extracellular matrix proteins in regulation of human glioma cell invasion in vitro.

    abstract::Primary brain tumors lack the metastatic behavior that is in part believed to be promoted by the extracellular matrix (ECM) components of the basement membrane. This study was intended to examine the influence of the ECM components present in the basement membrane that may act as natural barriers to tumor cell invasio...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Chintala SK,Gokaslan ZL,Go Y,Sawaya R,Nicolson GL,Rao JS

    更新日期:1996-09-01 00:00:00

  • An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential.

    abstract::To provide an investigative tool for the study of osteosarcoma (OSA) biology we have developed a syngeneic (balb/c) murine model of OSA, using cell lines derived from a spontaneously occurring murine OSA (Schmidt et al. Differentiation 1988; 39: 151-60). This model is characterized by orthotopic primary tumor growth, ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Khanna C,Prehn J,Yeung C,Caylor J,Tsokos M,Helman L

    更新日期:2000-01-01 00:00:00

  • Alterations in Cx43 and OB-cadherin affect breast cancer cell metastatic potential.

    abstract::Emerging evidence suggests that gap junctional intercellular communication (GJIC) and expression of connexins (Cx) contribute to the metastatic potential of breast cancer cells. To more directly address this, an aggressive bone metastasis breast cancer cell line, MDA-MET (MET), was stably transfected with human Cx43 c...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Li Z,Zhou Z,Donahue HJ

    更新日期:2008-01-01 00:00:00

  • Different sialyltransferase activities in human colorectal carcinoma cells from surgical specimens detected by specific glycoprotein and glycolipid acceptors.

    abstract::The amount and type of sialylation of tumor cell membranes depends on the activity of a number of different sialyltransferase enzymes. For the detection of specific activities in human colorectal carcinoma tissue several glycoprotein and glycolipid acceptors were used: desialylated fetuin, alpha 1-acid glycoprotein, b...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Kemmner W,Krück D,Schlag P

    更新日期:1994-05-01 00:00:00

  • Overview and update of the phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II) in melanoma.

    abstract::This short review offers an update on the first and second Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II) for patients with melanoma, and briefly traces the development of intraoperative lymphatic mapping and sentinel node biopsy. ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,多中心研究,评审


    authors: Morton DL

    更新日期:2012-10-01 00:00:00

  • Inhibition of metastasis in a murine 4T1 breast cancer model by liposomes preventing tumor cell-platelet interactions.

    abstract::The interaction between circulating tumor cells and blood components, mainly platelets, plays an important role during metastasis. In this study, we prepared liposomes containing the platelet aggregation inhibitor Cilostazol (Cil-L). The objective of this study was to investigate the effect of this Cil-L on platelet a...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Wenzel J,Zeisig R,Fichtner I

    更新日期:2010-01-01 00:00:00

  • The effect of down regulation of calcineurin Aα by lentiviral vector-mediated RNAi on the biological behavior of small-cell lung cancer and its bone metastasis.

    abstract::Bone is the third most common site of cancer metastasis. Over 30 to 40% of lung cancers can develop skeletal metastasis and no effective curative therapy exists in clinic cases. Previously we screened the different expression of proteins between SBC-5 cells and SBC-3 cells by proteomic study methods (MALDI-TOF/TOF-MS)...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Ma NQ,Liu LL,Min J,Wang JW,Jiang WF,Liu Y,Feng YG,Su HC,Feng YM,Zhang HL

    更新日期:2011-12-01 00:00:00

  • Comparative study on Lewis lung tumour lines with 'low' and 'high' metastatic capacity. III. Glycosaminoglycan synthesis, transport and degradation in cell lines.

    abstract::The glycosaminoglycans (GAGs) of low (LM) and highly metastatic (HM) cell lines of the Lewis lung tumour (3LL) were compared using [3H]glucosamine labelling techniques. The GAGs isolated from nuclei, cytoplasm, pericellular fractions and medium were analysed by cellulose acetate electrophoresis and by digestion with s...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Pogány G,Moczar E,Jeney A,Timár J,Timár F,Ditrói K,Lapis K

    更新日期:1989-11-01 00:00:00

  • Potentiation of cell invasion and matrix metalloproteinase production by alpha3beta1 integrin-mediated adhesion of gastric carcinoma cells to laminin-5.

    abstract::We previously reported that the adhesion of gastric carcinoma cells to the peritoneum mediated by the alpha3beta1 integrin-laminin interaction is a key step in the initial process of peritoneal metastatic dissemination. Carcinoma cells subsequently invade through the intercellular gaps of mesothelial linings. In this ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Saito Y,Sekine W,Sano R,Komatsu S,Mizuno H,Katabami K,Shimada K,Oku T,Tsuji T

    更新日期:2010-04-01 00:00:00

  • Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

    abstract::To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into ac...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,多中心研究


    authors: Bollen L,Wibmer C,Wang M,van der Linden YM,Leithner A,Bünger CE,Jensen AB,Fiocco M,Bratschitsch G,Pondaag W,Bovée JV,Dijkstra PD

    更新日期:2015-01-01 00:00:00

  • miR-200c inhibits invasion and migration in human colon cancer cells SW480/620 by targeting ZEB1.

    abstract::MicroRNAs are a class of ≈22-nt noncoding single-strand RNAs regulating gene expression postscriptionally. Metastasis caused poor prognosis in colorectal cancer patients and half of the patients developed metastatic lesions when admission. Here we investigated the possible roles of microRNAs in regulating metastasis i...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Chen ML,Liang LS,Wang XK

    更新日期:2012-06-01 00:00:00

  • Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell adhesion and metastasis in human umbilical cord vessel segment and in mouse model.

    abstract::Metastasis is the most devastating aspect of cancer and it is the main cause of morbidity and mortality in cancer patients. Tumor cell adhesion to the vascular endothelial cell lining is an important step in metastatic progression and is prompted by platelets. Mucin 1 is over-expressed and aberrantly glycosylated in m...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Sudha T,Phillips P,Kanaan C,Linhardt RJ,Borsig L,Mousa SA

    更新日期:2012-06-01 00:00:00

  • High-dose ionizing radiation-induced hematotoxicity and metastasis in mice model.

    abstract::Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been i...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Shin JW,Son JY,Raghavendran HR,Chung WK,Kim HG,Park HJ,Jang SS,Son CG

    更新日期:2011-12-01 00:00:00

  • Over-expression of human CD44s in murine 3T3 cells: selection against during primary tumorigenesis and selection for during micrometastasis.

    abstract::Human CD44 standard isoform (hCD44s) cDNA regulated by a high-expressing promoter was transfected into Balb/c 3T3 cells and the tumorigenic and metastatic capacities of the transfectants were investigated in nude mice at the subcutaneous site. One of three transfectants was tumorigenic. hCD44s expression was lost in t...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Kogerman P,Sy MS,Culp LA

    更新日期:1998-01-01 00:00:00

  • Phenotypic and functional characteristics of tumour-derived microvascular endothelial cells.

    abstract::We recently developed a method for the isolation and purification of tumour-derived endothelium. In this study the phenotypic and functional properties of human tumour-derived microvascular endothelial cells (TdMEC) were examined. Endothelium obtained from human adrenal gland specimens (HAMEC) was used as a reference ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Alessandri G,Chirivi RG,Fiorentini S,Dossi R,Bonardelli S,Giulini SM,Zanetta G,Landoni F,Graziotti PP,Turano A,Caruso A,Zardi L,Giavazzi R,Bani MR

    更新日期:1999-01-01 00:00:00

  • MTBP inhibits migration and metastasis of hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with increasing incidence. Despite curative surgical resection and advanced chemotherapy, its survival rate remains low. The presence of microvascular invasion and occult metastasis is one of the major causes for this poor outcome. MDM2 Binding...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Bi Q,Ranjan A,Fan R,Agarwal N,Welch DR,Weinman SA,Ding J,Iwakuma T

    更新日期:2015-04-01 00:00:00

  • Graded hypoxia modulates the invasive potential of HT1080 fibrosarcoma and MDA MB231 carcinoma cells.

    abstract::Spatial and temporal oxygen heterogeneity exists in most solid tumour microenvironments due to an inadequate vascular network supplying a dense population of tumour cells. An imbalance between oxygen supply and demand leads to hypoxia within a significant proportion of a tumour, which has been correlated to the likeli...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Subarsky P,Hill RP

    更新日期:2008-01-01 00:00:00

  • Breast cancer cells with inhibition of p38alpha have decreased MMP-9 activity and exhibit decreased bone metastasis in mice.

    abstract::p38 belongs to a family of mitogen-activated protein kinases, which transfer extracellular signals into intracellular responses. p38 is also frequently detected in clinical breast cancer specimens, but its role as a prognostic factor is not known. Of the various p38 isoforms, p38alpha has been shown to mediate the in ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Suarez-Cuervo C,Merrell MA,Watson L,Harris KW,Rosenthal EL,Väänänen HK,Selander KS

    更新日期:2004-01-01 00:00:00

  • Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice.

    abstract::Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight f...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Bar-Yehuda S,Farbstein T,Barer F,Ohana G,Fishman P

    更新日期:1999-01-01 00:00:00

  • Transparent reporting of experimental parameters in assays measuring phenotypic steps in metastasis.

    abstract::Metastasis is key to cancer mortality. Understanding its biology is vital for developing strategies to prevent and treat metastasis. Phenotypic assays to either study metastasis or evaluate anti-metastatic drugs are widely used in preclinical research. This technical note discusses the adherence of reporting essential...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Boiy R,Steenbrugge J,Van Deun J,Hendrix A,Meyer E,De Wever O

    更新日期:2018-12-01 00:00:00

  • Ras suppressor-1 promotes apoptosis in breast cancer cells by inhibiting PINCH-1 and activating p53-upregulated-modulator of apoptosis (PUMA); verification from metastatic breast cancer human samples.

    abstract::Metastasis, responsible for most deaths from breast cancer (BC), is a multistep process leading to cancer cell spread. Extracellular matrix (ECM)-related adhesion and apoptosis resistance play pivotal role in metastasis. Ras suppressor-1 (RSU-1) localizes to cell-ECM adhesions and binds to pro-survival adhesion protei...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Giotopoulou N,Valiakou V,Papanikolaou V,Dubos S,Athanassiou E,Tsezou A,Zacharia LC,Gkretsi V

    更新日期:2015-03-01 00:00:00

  • IL-4 and TNF-alpha induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells.

    abstract::The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of I...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Herzberg F,Schöning M,Schirner M,Topp M,Thiel E,Kreuser ED

    更新日期:1996-03-01 00:00:00

  • Improvements in population-based survival of patients presenting with metastatic rectal cancer in the south of the Netherlands, 1992-2008.

    abstract::We analysed population-based treatment and survival data of patients who presented with metastatic rectal cancer. All patients diagnosed with primary synchronous metastatic rectal cancer between 1992 and 2008 in the Eindhoven Cancer Registry area were included. Date of diagnosis was divided into three periods (1992-19...

    journal_title:Clinical & experimental metastasis

    pub_type: 历史文章,杂志文章


    authors: Lemmens VE,de Haan N,Rutten HJ,Martijn H,Loosveld OJ,Roumen RM,Creemers GJ

    更新日期:2011-03-01 00:00:00

  • RANK expression on breast cancer cells promotes skeletal metastasis.

    abstract::RANK ligand (RANKL), acting through its cognate receptor RANK, is a key factor for bone remodeling and metastasis by regulating the differentiation, survival and activation of osteoclasts. RANKL is also crucial for the development of mouse mammary glands during pregnancy and has been recently linked to the etiology of...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Blake ML,Tometsko M,Miller R,Jones JC,Dougall WC

    更新日期:2014-02-01 00:00:00

  • Resistance of the embryonic notochord to invasion by malignant neurogenic tumor cells in vitro.

    abstract::Very few tissues in vivo are resistant to invasion by malignant cells. In this paper, confrontation cultures consisting of chick embryonic notochord fragments and cell aggregates from three malignant neurogenic cell lines showed a resistance of the embryonic organ to malignant invasion by tumor cells. The mechanism of...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Schroyens W,Camon J,De Ridder L

    更新日期:1991-07-01 00:00:00

  • A chimeric antibody targeting CD147 inhibits hepatocellular carcinoma cell motility via FAK-PI3K-Akt-Girdin signaling pathway.

    abstract::CD147 is expressed at low levels in normal tissues but frequently highly expressed in a wide range of tumor types such as lung, breast, and liver and therefore it is a potentially unique therapeutic target for these diverse tumor types. We previously generated a murine antibody HAb18 which suppresses matrix met al.lop...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Wang Y,Yuan L,Yang XM,Wei D,Wang B,Sun XX,Feng F,Nan G,Wang Y,Chen ZN,Bian H

    更新日期:2015-01-01 00:00:00

  • Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer.

    abstract::Matrilysin is a member of the matrix metalloproteinase gene family which is believed to play an important role in tumor progression. Expression of matrilysin mRNA was examined by reverse transcription-polymerase chain reaction combined with Southern blot analysis in 46 human primary gastric cancers. Overexpression of ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Senota A,Itoh F,Yamamoto H,Adachi Y,Hinoda Y,Imai K

    更新日期:1998-05-01 00:00:00

  • Inhibition of colony formation in agarose of metastatic human breast carcinoma and melanoma cells by synthetic glycoamine analogs.

    abstract::We studied the influence of 10 synthetic glycoamine analogs on colony formation in 0.3 and 0.9% agarose by metastatic human breast carcinoma (MDA-MB-435) and melanoma (TXM-13) cells. Nine synthetic analogs significantly inhibited the colony formation in 0.9% agarose of MDA-MB-435 human breast carcinoma cells; five com...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Glinsky GV,Mossine VV,Price JE,Bielenberg D,Glinsky VV,Ananthaswamy HN,Feather MS

    更新日期:1996-05-01 00:00:00

  • Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas.

    abstract::This study examined the relationship between the expression of E-cadherin or beta-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, M...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Akimoto T,Kawabe S,Grothey A,Milas L

    更新日期:1999-03-01 00:00:00

  • Influence of the host microenvironment on the clonal selection of human colon carcinoma cells during primary tumor growth and metastasis.

    abstract::The purpose of this study was to determine the subpopulation dynamics of human colon carcinoma (HCC) cells growing at orthotopic (cecum, liver) or ectopic (subcutis, kidney, spleen) sites in nude mice and to correlate any outgrowth of distinct clones with the differential expression of metastasis-related genes. Low me...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Singh RK,Tsan R,Radinsky R

    更新日期:1997-03-01 00:00:00