Colon cancer cell adhesion in response to Src kinase activation and actin‐cytoskeleton by non‐laminar shear stress

Thamilselvan, Vijayalakshmi; Patel, Ashish; Zyp, J. van der Voort van; Basson, Marc D.

doi:10.1002/jcb.20072

Cited by 34 publications

(29 citation statements)

References 48 publications

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“…FSS has also been shown to induce changes in the gene expression, cytoskeletal, and adhesive properties of both leukocytes and cancer cells [32][33][34][35]. Here we found that FSS-naïve carcinoma cells exhibited a greater loss of cell viability in the first one to two passages, comparable to that measured in primary cells, but in subsequent passages, cell loss moderated, producing a biphasic viability curve.…”

Section: Discussionsupporting

confidence: 60%

Novel Biophysical Marker of Aggressive Prostate Cancer Cells

Henry¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 5f. WORK UNIT NUMBER REPORT DATE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Iowa College of Medicine PERFORMING ORGANIZATION REPORT NUMBERIowa City, Iowa 52242 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe most significant finding of this research study during this period is the validation of resistance to fluid shear stress as a biomarker of prostate cancer cells. This initial finding has been published. Additional efforts have been undertaken to detect this biomarker in circulating tumor cells from blood samples from prostate cancer patients. This involves the development of methods to achieve this goal. Figure 2. We have applied this approach to an initial set of 3 prostate cancer patients in which a blood sample was taken 1d prior to prostatectomy and 1d post-operative. These initial findings are summarized in Figure 3. These findings are encouraging and suggest that CTCs are detectable by this method at the time of prostatectomy. In principle, our assay for FSS resistance could be applied at this time and this biomarker may indicate the degree to which these cells have the propensity to progress to metastasis. Additional findings are that very few cells detected are double-positive for EpCAM and N-Cadherin, and there is a possibility that CTC numbers increase from pre-operative to post-operative day 1, suggesting that surgical manipulation may increase CTC numbers in this setting. However, these findings are highly preliminary at this point. Additional studies are underway to confirm the identity of these cells as prostate CTC's by staining for PSA and/or PSMA. SUBJECT TERMSSOW 1c. Accrue and analyze patient samples (Months 9-23) As noted above, 3 patients have been accrued in the validation portion of this proposal. Once we have established that the cells we are measuring ate bona-fide prostate cancer CTCs, we will ...

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Section: Discussionsupporting

confidence: 60%

Novel Biophysical Marker of Aggressive Prostate Cancer Cells

Henry¹

2013

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“…We have previously reported that a pathophysiologically relevant (15 mmHg) increase in extracellular pressure stimulates colon cancer cell adhesion to matrix proteins, endothelial cell monolayers, and surgical wounds in vivo by a ␤ 1 -integrin-dependent mechanism (2,58,64). Nonlaminar shear has a similar effect (61). Pressure stimulates cell adhesion to collagen, fibronectin, laminin, and Matrigel (2,26), suggesting that this effect is not restricted to a specific ␣/␤ 1 -integrin heterodimer pair.…”

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confidence: 94%

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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“…At least one pathway by which this occurs seems to involve focal adhesion kinase (FAK) and Src activation (2) and paxillin (6,7) and has been shown to be active in breast (8), head and neck (6), and colon (1) cancer cell lines, as well as in primary human colon cancer cells isolated directly from surgical specimens (2). These signals mediating increased adhesion are stimulated by increased extracellular pressure (2) as well as by laminar or nonlaminar shear stress (4,5,9).…”

Section: Introductionmentioning

confidence: 99%

An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces

Basson

2008

Cancer Research

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Increasing evidence suggests that tumor cells can regulate their own adhesion via intracellular signals that modulate integrin binding affinity. Although the full pathway has not yet been elucidated, the effects of pressure seem likely to require cytoskeletal mechanosensing, Src, phosphatidylinositol 3-kinase, focal adhesion kinase, and Akt-1 activation. Ultimately, activated focal adhesion kinase accumulates at the membrane in association with B 1

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Colon cancer cell adhesion in response to Src kinase activation and actin‐cytoskeleton by non‐laminar shear stress

Cited by 34 publications

References 48 publications

Novel Biophysical Marker of Aggressive Prostate Cancer Cells

Novel Biophysical Marker of Aggressive Prostate Cancer Cells

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

An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces

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Colon cancer cell adhesion in response to Src kinase activation and actin‐cytoskeleton by non‐laminar shear stress

Cited by 34 publications

References 48 publications

Novel Biophysical Marker of Aggressive Prostate Cancer Cells

Novel Biophysical Marker of Aggressive Prostate Cancer Cells

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

An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces

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