Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice

Craig, David; Owen, Cheri R.; Conway, William G.; Walsh, Mary F.; Downey, Christina; Basson, Marc D.

doi:10.1172/jci34279

Cited by 39 publications

(47 citation statements)

References 54 publications

(61 reference statements)

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“…Exposure to these forces may influence the ability of shed cells to adhere and form new tumors. Although metastasis may also require cell invasion, we recently reported that a 30-min exposure to 15-mmHg increased pressure does not affect tumor cell invasion in a Boyden-chamber assay (10). Although these results do not exclude an effect of physical forces on tumor cell motility, brief increases in extracellular pressure seem to affect tumor cell adhesion more importantly than tumor cell motility.…”

Section: Discussionmentioning

confidence: 75%

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789

Craig¹,

Gayer²,

Schaubert³

et al. 2009

American Journal of Physiology-Cell Physiology

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. Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of ␤1-integrin at threonine 788/789. Am J Physiol Cell Physiol 296: C193-C204, 2009. First published November 12, 2008 doi:10.1152/ajpcell.00355.2008.-Increased extracellular pressure stimulates ␤1-integrin-dependent cancer cell adhesion. We asked whether pressure-induced adhesion is mediated by changes in ␤1-integrin binding affinity or avidity and whether these changes are phosphorylation dependent. We evaluated integrin affinity and clustering in human SW620 colon cancer cells by measuring differences in binding between soluble Arg-Gly-Asp (RGD)-Fc ligands and RGD-Fc-F(abЈ)2 multimeric complexes under ambient and 15-mmHg increased pressures. Phosphorylation of ␤1-integrin S785 and T788/9 residues in SW620 and primary malignant colonocytes was assessed in parallel. We further used GD25-␤1-integrin-null murine fibroblasts stably transfected with either wild-type ␤1A-integrin, S785A, TT788/9AA, or T788D mutants to investigate the role of ␤1-integrin site-specific phosphorylation. SW620 binding of RGD-Fc-F(abЈ)2 multimeric complexes, but not soluble RGD-Fc ligands, was sensitive to integrin clustering. RGD-Fc ligand binding was significantly increased under elevated pressure, suggesting that pressure modulates ␤1-integrin affinity. Pressure stimulated both ␤1-integrin S785 and T788/9 phosphorylation. GD25-␤1A-integrin wild-type and S785A cells displayed an increase in adhesion to fibronectin under elevated pressure, an effect absent in ␤1-integrin-null and TT788/9AA cells. T788D substitution significantly elevated basal cell adhesion but displayed no further increase under pressure. These results suggest pressure-induced cell adhesion is mediated by ␤1-integrin T788/9 phosphorylation-dependent changes in integrin binding affinity. adhesion; mechanotransduction; metastasis INTEGRIN-MEDIATED TUMOR CELL adhesion to extracellular matrix components or endothelial cells is an important step in the development of metastatic lesions. Integrin binding affinity is regulated by distinct receptor activation states (23). Initial cell attachment requires integrin activation by cytoplasmic signals that convey large conformational changes to the extracellular domain and enhance ligand-binding affinity (56). The avidity and strength of the interaction is further increased through the redistribution of integrins in the cell membrane, often referred to as receptor clustering (65). The tendency of some malignancies to exhibit reduced integrin expression while maintaining adhesive properties underscores the significance of integrin activation states in mediating tumor cell adhesion (33, 47).Likewise, mutations conferring constitutive integrin activation have been shown to directly contribute to the metastatic potential of cancer cells (20,53). Mechanisms underlying integrin affinity and avidity modulation are therefore of significant interest in the control of tumor metastasis.It is increasingly clear that integrin modulation may...

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Section: Discussionmentioning

confidence: 75%

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789

Craig¹,

Gayer²,

Schaubert³

et al. 2009

American Journal of Physiology-Cell Physiology

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“…Prolonged exposure to elevated mechanical pressure has been shown to diminish apoptosis 51 and stimulate cell division 52 of some tumor cells and, moreover, can decrease survival duration in some tumor models. 53 It is widely appreciated that the outcome of metastasis is determined by the interactions that take place between specific populations of metastatic cells and their organ microenvironment. 1 The results of the present studies with GI-101A breast cancer cells indicate that the hard agar assay selects for cells that are capable of growth in multiple target organs of breast metastasis (brain, liver, lung).…”

Section: Discussionmentioning

confidence: 99%

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

Guo

Fan

Zhang

et al. 2011

The American Journal of Pathology

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An approach that facilitates rapid isolation and characterization of tumor cells with enhanced metastatic po-The vast majority of cancer deaths result from progressive growth of metastases that are resistant to conventional therapies. 1 Metastases originate from a selected subpopulation of cells that reside in a biologically heterogeneous primary tumor. 2,3 Results from experimental 4 and clinical 5 examinations indicate that most metastases are clonal in origin and that the metastatic process is highly selective. 6 Studies have also shown profound differences between local and disseminated cancers, 7 suggesting that information on primary tumors alone may not be sufficient to determine optimal therapeutic interventions. For this reason, researchers have directed considerable effort toward improving understanding of the molecular phenotypes of metastasis-initiating tumor cells.One widely used experimental approach to isolate populations of tumor cells with enhanced metastatic potential is an in vivo selection process in which tumor cells are implanted into syngeneic or immunodeficient mice and metastasis is allowed to occur. Tumor cells from the resultant metastatic lesions can be isolated and expanded to establish cell sublines, some of which may have higher metastatic capacity than the parental tumorcell population. 8 Comparative gene expression profiling of parental tumor cells and their metastatic subpopulations has yielded invaluable information regarding the genetic determinants critical for organ-specific metastasis. 9 For example, Kang et al 10 compared the transcriptional profiles of parental MDA-231 human breast cancer cells with those of a bone-colonizing variant of this cell line and reported the underlying gene expression signature required for organ tropism to bone. Investigators used a similar approach to identify genes whose expression is critical for metastasis of breast cancer cells to the brain 11 and lungs. 12 Nevertheless, although this in vivo selection technique has provided new insight into the cellular and molecular mechanisms that control site-specific metastasis, there are some disadvantages. Perhaps the principal drawback of in vivo selection is that it can be time-consuming,

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“…Colchicine therapy improved BMI slightly, but significantly (Tukmen et al, 2008). Pressure activation of malignant cells promotes tumor development and impairs tumor-free survival and perioperative colchicine administration may inhibit this effect (Craig et al, 2008). The usage of colchicine is restricted because of its toxicity, possibly because of its poor purity and because the toxicity studies on colchicine derivatives such as 2-demethyl colchicine, 3-demethyl colchicine and N-formyl-Ndeacetylcolchicine have not been confirmed till now.…”

Section: Introductionmentioning

confidence: 99%

Isolation and anti-inflammatory activity of colchicinoids fromGloriosa superbaseeds

Joshi

Ekambaram

Mathela

2009

Pharmaceutical Biology

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Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice

Cited by 39 publications

References 54 publications

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

Isolation and anti-inflammatory activity of colchicinoids fromGloriosa superbaseeds

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Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice

Cited by 39 publications

References 54 publications

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β1-integrin at threonine 788/789

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β1-integrin at threonine 788/789

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

Isolation and anti-inflammatory activity of colchicinoids fromGloriosa superbaseeds

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Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789