Fluid shear- and time-dependent modulation of molecular interactions between PMNs and colon carcinomas

Jadhav, Sameer; Κωνσταντόπουλος, Κωνσταντίνος

doi:10.1152/ajpcell.00104.2002

Cited by 63 publications

(61 citation statements)

References 35 publications

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“…This finding may provide a basis for interpreting experimental observations showing the existence of an intermediate shear rate at which maximal homotypic PMN aggregation occurs (Taylor, et al, 1996;Jadhav, et al, 2001;Jadhav and Konstantopoulos, 2002;Simon and Goldsmith, 2002;Kadash, et al, 2004). However, recent experimental observations also suggest that selectins exhibit a "catch-slip" bond transition, where increasing tensile forces initially prolong, and subsequently diminish bond lifetimes (Marshall, et al, 2003;Yago, et al, 2004).…”

Section: Resultsmentioning

confidence: 65%

Shear modulation of intercellular contact area between two deformable cells colliding under flow

Jadhav

Chan

Κωνσταντόπουλος

et al. 2007

Journal of Biomechanics

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Shear rate has been shown to critically affect the kinetics and receptor specificity of cell-cell interactions. In this study, the collision process between two modeled cells interacting in a linear shear flow is numerically investigated. The two identical biological or artificial cells are modeled as deformable capsules composed of an elastic membrane. The cell deformation and trajectories are computed using the Immersed Boundary Method for shear rates of 100-400 s −1 . As the two cells collide under hydrodynamic shear, large local cell deformations develop. The effective contact area between the two cells is modulated by the shear rate, and reaches a maximum value at intermediate levels of shear. At relatively low shear rate, the contact area is an enclosed region. As the shear rate increases, dimples form on the membrane surface, and the contact region becomes annular. The nonmonotonic increase of the contact area with the increase of shear rate from computational results implies that there is a maximum effective receptor-ligand binding area for cell adhesion. This finding suggests the existence of possible hydrodynamic mechanism that could be used to interpret the observed maximum leukocyte aggregation in shear flow. The critical shear rate for maximum intercellular contact area is shown to vary with cell properties such as radius and membrane elastic modulus.

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Section: Resultsmentioning

confidence: 65%

Shear modulation of intercellular contact area between two deformable cells colliding under flow

Jadhav

Chan

Κωνσταντόπουλος

et al. 2007

Journal of Biomechanics

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“…54 It has been shown in vitro that stationary neutrophils can facilitate tumor cell arrest and transmigration across endothelial monolayers via binding interactions between adherent neutrophils and passing tumor cells that are both adhesion molecule-and shear rate-dependent. 30,31,55,56 In vivo, we found that systemic inflammation increased tumor cell recruitment in the liver sinusoids when leukocytes simultaneously adhered in these vessels. Indeed, almost 80% of tumor cells were colocalized with adherent neutrophils in the sinusoids of LPS inflamed mice.…”

Section: Discussionmentioning

confidence: 84%

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

McDonald

Spicer

Giannais

et al. 2009

Intl Journal of Cancer

197

162

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Interactions between endothelial selectins and selectin ligands expressed on tumor cells have been implicated in the binding of circulating metastatic cancer cells to the vascular endothelium during extravasation. Moreover, there is mounting evidence that inflammatory environments can accelerate the progression of metastasis by neutrophil mediated mechanisms. In this study, a physiologically relevant in vivo model of early metastasis coupled with intravital microscopy was used to visualize the trafficking of tumor cells within the liver vasculature in real time. Using GFPlabeled Lewis lung carcinoma subline H-59 cells, we show here that disrupting the interactions between endothelial selectins and tumor cell selectin ligands diminished tumor cell recruitment to the liver. Furthermore, systemic inflammation induced by intravenous injection of lipopolysaccharide significantly enhanced the metastatic potential of these lung carcinoma cells by increasing their propensity to adhere to the liver sinusoidal endothelium. Confocal microscopy revealed frequent colocalization of cancer cells with neutrophils and neutrophil depletion in vivo significantly attenuated the lipopolysaccharide-induced increase in H-59 cell adhesion. Although direct selectin-selectin ligand interactions contributed significantly to tumor cell adhesion to sinusoidal endothelial cells, we show here that in addition, interactions between adherent neutrophils within the inflamed sinusoids and circulating tumor cells may further increase tumor cell arrest in the liver. ' 2009 UICC Key words: cancer; metastasis; lung; rodent; adhesion molecules; e-selectin; neutrophil; sialyl Lewis X Lung cancer is the leading cause of cancer-related deaths worldwide. 1 A high proportion of patients harbor metastasis to regional lymph nodes upon presentation, and over half of all patients who undergo curative intent surgical resection of the lung will develop metastatic recurrence. 2 The liver is a common site of metastasis for lung cancer, with autopsy studies showing hepatic metastases in over 50% of lung cancer patients. 3 The hematogenous dissemination of cancer cells from a primary tumor to distant organs involves a cascade of sequential steps (reviewed in Refs. 4,5). The adhesion of circulating tumor cells to the vascular endothelium of distant organs is a key step in the metastatic cascade that may determine the organ tropism and extent of metastasis. Interactions between endothelial selectins and tumor cell selectin ligands have been implicated in the metastatic process. [5][6][7][8] Selectins are a family of transmembrane glycoproteins possessing an extracellular lectin domain that binds to carbohydrate moieties present on their ligands. 9 The three known selectins that function as cell adhesion molecules are expressed on the surface of endothelial cells (E-selectin and P-selectin), platelets (P-selectin) and leukocytes (L-selectin). E-selectin has been shown to contribute to the metastatic spread of multiple cancers, including lung and colon carcinoma, and m...

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“…Cells were detached from culture flasks using 0.25% trypsin, EDTA for 2 min at 37°C (5,10,21,22). For force spectroscopy experiments, 20 l of 1 ϫ 10 7 cells/ml LS174T cell suspension was layered on 35-mm tissue culture dishes and subsequently incubated overnight at 37°C to allow adhesion to the culture dish and regeneration of surface glycoproteins (5,10).…”

Section: Methodsmentioning

confidence: 99%

Single Molecule Characterization of P-selectin/Ligand Binding

Hanley

McCarty²,

Jadhav³

et al. 2003

Journal of Biological Chemistry

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175

210

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P-selectin expressed on activated platelets and vascular endothelium mediates adhesive interactions to polymorphonuclear leukocytes (PMNs) and colon carcinomas critical to the processes of inflammation and bloodborne metastasis, respectively. How the overall adhesiveness (i.e. the avidity) of receptor/ligand interactions is controlled by the affinity of the individual receptors to single ligands is not well understood. Using single molecule force spectroscopy, we probed in situ both the tensile strength and off-rate of single P-selectin molecules binding to single ligands on intact human PMNs and metastatic colon carcinomas and compared them to the overall avidity of these cells for P-selectin substrates. The use of intact cells rather than purified proteins ensures the proper orientation and preserves post-translational modifications of the P-selectin ligands. The P-selectin/PSGL-1 interaction on PMNs was able to withstand forces up to 175 pN and had an unstressed off-rate of 0.20 s ؊1 . The tensile strength of Pselectin binding to a novel O-linked, sialylated proteasesensitive ligand on LS174T colon carcinomas approached 125 pN, whereas the unstressed off-rate was 2.78 s ؊1 . Monte Carlo simulations of receptor/ligand bond rupture under constant loading rate for both Pselectin/PSGL-1 and P-selectin/LS174T ligand binding give distributions and mean rupture forces that are in accord with experimental data. The pronounced differences in the affinity for P-selectin/ligand binding provide a mechanistic basis for the differential abilities of PMNs and carcinomas to roll on P-selectin substrates under blood flow conditions and underline the requirement for single molecule affinity measurements.Cellular adhesion mediated by biological macromolecules and their respective ligands plays an essential role in a number of diverse biological phenomena including inflammation and cancer metastasis. Leukocyte recruitment to sites of infection is regulated by highly specific receptor/ligand interactions that allow leukocytes to first tether and roll on activated endothelium under hydrodynamic shear and then firmly adhere prior to extravazation into the tissue space. These stages are mediated via three distinct classes of adhesion molecules: the selectins, integrins, and immunoglobulins (1-3). Accumulating evidence suggests that tumor cell arrest in the microcirculation is also mediated through receptor/ligand interactions between tumor cells and the vascular endothelium in a manner analogous to leukocyte recruitment (4 -6). Both processes involve highly regulated molecular events that rely on the local circulatory hemodynamics and the mechanical and kinetic properties of participating adhesive molecular groups, which have yet to be characterized at the single molecule level.The involvement of P-selectin is critical within immune system functioning. P-selectin, a cell-surface glycoprotein expressed on activated endothelial cells and platelets, supports leukocyte tethering and rolling in response to inflammatory signals by interac...

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Fluid shear- and time-dependent modulation of molecular interactions between PMNs and colon carcinomas

Cited by 63 publications

References 35 publications

Shear modulation of intercellular contact area between two deformable cells colliding under flow

Shear modulation of intercellular contact area between two deformable cells colliding under flow

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

Single Molecule Characterization of P-selectin/Ligand Binding

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