Mechanisms of tumour metastasis

Meyer, Tim; Hart, I. R.

doi:10.1016/s0959-8049(97)10129-0

Cited by 164 publications

(92 citation statements)

References 76 publications

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“…As pointed out above, the clinical options for advanced melanoma are still limited, due to the intrinsic resistance of the tumor to standard chemotherapy, but also to its ability to give rise to metastases (Meyer & Hart 1998). The data here reported seem to suggest that LHRH agonists might reduce not only the proliferation rate, but also the metastatic potential of melanoma cells (see Fig.…”

Section: Antimetastatic Activity Of Lhrhsupporting

confidence: 56%

Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression.

Moretti

Marelli²,

Groeninghen³

et al. 2003

Endocrine-Related Cancer

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Luteinizing hormone-releasing hormone (LHRH) is the key hormone in the control of reproductive functions. In recent years, it has become evident that LHRH might act as a growth modulatory factor in tumors of the reproductive system. We have shown that in prostate cancer cells LHRH is expressed, together with its receptors, to negatively regulate cell proliferation. In these cells, LHRH acts as an antimitogenic factor through the activation of the Gi-cAMP intracellular signaling pathway. More recently, we investigated whether an LHRH-based autocrine system might also be expressed in tumors that are not classically related to the reproductive tract, such as melanoma. Malignant melanoma is known to be characterized not only by a high proliferation rate, but also by an aggressive metastatic behavior. We have demonstrated that both LHRH and LHRH receptors are expressed in human melanoma cells (BLM and Me15392). Activation of LHRH receptors by means of a potent LHRH agonist (Zoladex) significantly inhibited cell proliferation. The LHRH agonist also reduced the ability of melanoma cells to invade a reconstituted basement membrane (Matrigel) and to migrate in response to a chemotactic stimulus. These data indicate that: (a) in prostate cancer cells the LHRH receptor is coupled to a Gi-cAMP signal transduction pathway; (b) LHRH and LHRH receptors are also expressed in tumors that are not classically related to the reproductive system, such as melanoma; in melanoma cells, LHRH might act as an inhibitory factor on both cell proliferation and metastatic behavior. It is suggested that, in melanoma, LHRH receptors might represent a diagnostic marker and a possible molecular target for new therapeutic approaches for this pathology.

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Section: Antimetastatic Activity Of Lhrhsupporting

confidence: 56%

Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression.

Moretti

Marelli²,

Groeninghen³

et al. 2003

Endocrine-Related Cancer

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“…During invasion, metastatic cancer cells exhibit deregulation of adhesive properties to the neighbouring cells and extracellular matrix, and present motility and secretion of matrix-degrading enzymes. 1 It is possible that these phenomena are caused by modifications of the contractile machineries, which normally power these functions in nonmalignant cells. In this study we determined if myosin II, the conventional myosin, played a role in regulating the invasion process of metastatic cancer cells by inhibiting myosin II function with myosin light chain kinase (MLCK) inhibitors and assessing the effects on the cell invasiveness in vitro.…”

Section: Introductionmentioning

confidence: 99%

Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain

Tohtong

Phattarasakul

Jiraviriyakul

et al. 2003

Prostate Cancer Prostatic Dis

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The role of myosin phosphorylation by myosin light chain kinase (MLCK) in regulating the invasiveness of metastatic cancer cells was investigated using the Dunning rat prostatic adenocarcinoma cell line, Mat Ly Lu, and in vitro invasion assay. Treatment with MLCK inhibitors resulted in marked reduction of invasiveness, which was principally due to impaired cellular motility, whereas the ability to survive and proliferate, to adhere to matrix, and to secrete gelatinases were minimally affected.

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“…1,2 The metastatic process consists of multiple steps: (i) dissociation of tumor cell(s) from the primary site with a concomitant loss of cell-cell and cell-extracellular matrix (ECM) adhesions; (ii) tumor-cell adhesion to and subsequent local digestion of basement membrane; (iii) retraction of endothelial cells and subsequent intravasation; (iv) survival within the vasculature; (v) extravasation from vasculature at a distant site and (vi) growth in a "foreign" or ectopic organ environment. 3,4 Much attention has been paid to the interaction of cell-cell or cell-ECM adhesion [5][6][7] and to proteolysis by a variety of classes of degradative enzymes and their inhibitors, 8,9 even though tumor cell migration is also an essential step for establishment of cancer metastasis. It is well known that the actin cytoskeleton is a major component of the cell motility machinery.…”

mentioning

confidence: 99%

Gelsolin functions as a metasatsis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect

et al. 2001

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Gelsolin, an actin-binding protein, is implicated as a critical regulator in cell motility. In addition, we have reported that cellular levels of gelsolin are decreased in various tumor cells, and overexpression of gelsolin by gene transfer suppresses tumorigenicity. We sought to assess the effects of gelsolin overexpression on metastasis and to determine the importance of a carboxyl-terminus that confers Ca 2؉ dependency on gelsolin for effects of its overexpression. Expression vectors with cDNA encoding either full-length wild-type or His321 mutant form, isolated from a flat revertant of Rastransformed cells and a carboxyl-terminal truncate, C-del of gelsolin, were transfected into a highly metastatic murine melanoma cell line, B16-BL6. Expression of introduced cDNA in transfectants was confirmed using Western blotting, 2-dimensional gel electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). We characterized phenotypes of transfectants, such as growth rate, colony formation in soft agar, cell motility and metastasis formation in vivo. Transfectants expressing the wild-type, His321 mutant and C-del gelsolin exhibited reduced growth ability in soft agar. Although expression of integrin ␤1 or ␣4 on the cell surface of transfectants was not changed, wild-type and His321 mutant gelsolin, except for C-del gelsolin, exhibited retardation of cell spreading, reduced chemotatic migration to fibronectin and suppressed lung colonization in spontaneous metastasis assay. Gelsolin may function as a metastasis suppressor as well as a tumor suppressor gene. The carboxylterminus of gelsolin is important for retardation of cell spreading, reduced chemotasis and metastasis suppression. © 2001 Wiley-Liss, Inc. Key words: gelsolin; metastasis; cell spreading; cell motilityMetastasis, the spread of malignant tumor cells from a primary site to distant sites, is the most life-threatening complication of cancer and a major problem of cancer treatment. 1,2 The metastatic process consists of multiple steps: (i) dissociation of tumor cell(s) from the primary site with a concomitant loss of cell-cell and cell-extracellular matrix (ECM) adhesions; (ii) tumor-cell adhesion to and subsequent local digestion of basement membrane; (iii) retraction of endothelial cells and subsequent intravasation; (iv) survival within the vasculature; (v) extravasation from vasculature at a distant site and (vi) growth in a "foreign" or ectopic organ environment. 3,4 Much attention has been paid to the interaction of cell-cell or cell-ECM adhesion [5][6][7] and to proteolysis by a variety of classes of degradative enzymes and their inhibitors, 8,9 even though tumor cell migration is also an essential step for establishment of cancer metastasis. It is well known that the actin cytoskeleton is a major component of the cell motility machinery. 10,11 Evidence is accumulating that changes in actin cytoskeletal organization, adhesiveness and motility are important not only for tumor development and progression but also may be critical for deter...

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Mechanisms of tumour metastasis

Cited by 164 publications

References 76 publications

Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression.

Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression.

Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain

Gelsolin functions as a metasatsis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect

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