Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength

DiMilla, Paul A.; Ja, Stone; Quinn, J.A.; Albelda, Steven; Lauffenburger, Douglas A.

doi:10.1083/jcb.122.3.729

Cited by 569 publications

(512 citation statements)

References 33 publications

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“…Our findings suggest that the role of Sema3A in GBM migration/dispersal is complex and perhaps biphasic. There is a biphasic relationship between the adhesive strength and cell motility of cells such that there is optimal adhesion for maximal cell motility (DiMilla et al, 1993;Cox and Huttenlocher, 1998). Similarly, our findings are consistent with an optimal Sema3A concentration for GBM dispersal such that GBM cells are able to release their adhesions efficiently and move away from one another.…”

Section: Discussionsupporting

confidence: 87%

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

et al. 2009

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Glioblastoma multiforme (GBM) is the most malignant glioma type with diffuse borders due to extensive tumor cell infiltration. Therefore, understanding the mechanism of GBM cell dispersal is critical for developing effective therapies to limit infiltration. We identified neuropilin-1 as a mediator of cancer cell invasion by a functional proteomic screen and showed its role in GBM cells. Neuropilin-1 is a receptor for semaphorin3A (Sema3A), a secreted chemorepellent that facilitates axon guidance during neural development. Although neuropilin-1 expression in GBMs was previously shown, its role as a Sema3A receptor remained elusive. Using fluorophore-assisted light inactivation and RNA interference , we showed that neuropilin-1 is required for GBM cell migration. We also showed that GBM cells secrete Sema3A endogenously, and RNA interferencemediated downregulation of Sema3A inhibits migration and alters cell morphology that is dependent on Rac1 activity. Sema3A depletion also reduces dispersal, which is recovered by supplying Sema3A exogenously. Extracellular application of Sema3A decreases cell-substrate adhesion in a neuropilin-1-dependent manner. Using immunohistochemistry, we showed that Sema3A is overexpressed in a subset of human GBMs compared with the non-neoplastic brain. Together, these findings implicate Sema3A as an autocrine signal for neuropilin-1 to promote GBM dispersal by modulating substrate adhesion and suggest that targeting Sema3A-neuropilin-1 signaling may limit GBM infiltration.

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Section: Discussionsupporting

confidence: 87%

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

et al. 2009

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“…Cell migratory ability can be also determined by the absolute concentrations of ECM components: this mechanism is called haptokinesis. At this regard, several experimental studies show that cell speed, spreading, and membrane activity is maximal at intermediate levels of ECM densities, both on 2D substrates [14,19] and in 3D matrices [73]. Also the local rigidity of the matrix plays a fundamental role in determining the efficiency and the direction of cell crawling, e.g.…”

Section: Discussionmentioning

confidence: 99%

A cellular Potts model analyzing differentiated cell behavior during in vivo vascularization of a hypoxic tissue

Scianna

Bassino

Munaron

2015

Computers in Biology and Medicine

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Angiogenesis, the formation of new blood vessel networks from existing capillary or post-capillary venules, is an intrinsically multiscale process occurring in several physio-pathological conditions. In particular, hypoxic tissue cells activate downstream cascades culminating in the secretion of a wide range of angiogenic factors, including VEGF isoforms. Such diffusive chemicals activate the endothelial cells (ECs) forming the external walls of the nearby vessels, that chemotactictally migrate toward the hypoxic areas of the tissue as multicellular sprouts. A functional network eventually emerges by further branching and anastomosis processes. We here propose a CPM-based approach reproducing selected features of the angiogenic progression necessary for the reoxygenation of a hypoxic tissue. Our model is able to span the different scale involved in the angiogenic progression as it incorporates reaction-diffusion equations for the description of the evolution of microenvironmental variables in a discrete mesoscopic cellular Potts model (CPM) that reproduces the dynamics of the vascular cells. A key feature of this work is the explicit phenotypic differentiation of the ECs themselves, distin-1 E-Mail: marcosci1@alice.it 2 E-Mail: eleonora.bassino@unito.it 3 E-Mail: luca.munaron@unito.it Preprint submitted to Computers in Biology and Medicine May 25, 2015 guished in quiescent, stalk and tip. The simulation results allow identifying a set of key mechanisms underlying tissue vascularization. Further, we provide evidence that the nascent pattern is characterized by precise topological properties. Finally, we link abnormal sprouting angiogenesis with alteration in selected cell behavior.

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“…Although this work did not determine whether the MMP-1 was bound to the ␣ 2 ␤ 1 or ␣ 1 ␤ 1 integrins, the finding is entirely consistent with the model we have presented in this report. Indeed, it has been shown that an intermediate level of integrin expression is required for optimal migration (43). If levels are too low, the cell cannot gain traction; if levels are too high, presumably the cell becomes too firmly attached to the matrix.…”

Section: Figmentioning

confidence: 99%

Structural Analysis of the α2 Integrin I Domain/Procollagenase-1 (Matrix Metalloproteinase-1) Interaction

Stricker¹,

Dumin²,

Dickeson³

et al. 2001

Journal of Biological Chemistry

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Previous studies have established that ligation of keratinocyte ␣ 2 ␤ 1 integrin by type I collagen induces expression of matrix metalloproteinase-1 (MMP-1) and that MMP-1 activity is required for the ␣ 2 ␤ 1 integrin-dependent migration of primary keratinocytes across collagenous matrices. We now present evidence that MMP-1 binds the ␣ 2 ␤ 1 integrin via the I domain of the ␣ 2 integrin subunit. Using an enzyme-linked immunosorbent assay with purified human MMP-1 and recombinant ␣ 2 integrin I domain, we showed that the ␣ 2 integrin I domain specifically bound in a divalent cation-dependent manner to both the pro and active forms of MMP-1, but not to MMP-3 or MMP-13. Although both the I domain and MMP-1 bind divalent cations, MMP-1 bound, in a divalent cation-dependent manner, to ␣ 2 integrin I domains containing metal ion-dependent adhesion sites motif mutations that prevent divalent cation binding to the I domain, demonstrating that the metal ion dependence is a function of MMP-1. Using a series of MMP-1-MMP-3 and MMP-1-MMP-13 chimeras, we determined that both the linker domain and the hemopexin-like domain of MMP-1 were required for optimal binding to the I domain. The ␣ 2 integrin/MMP-1 interaction described here extends an emerging paradigm in matrix biology involving anchoring of proteinases to the cell surface to regulate their biological activities.The extracellular matrix is not a static environment. Remodeling and degradation of the extracellular matrix is a vital component of physiological and pathophysiological processes, such as development and differentiation, cell migration, angiogenesis, wound healing, and metastasis. Matrix metalloproteinases (MMPs) 1 play a central role in the turnover of extracellular matrix components (1).MMPs constitute a large family of metal-dependent endoproteases with varying substrate specificities for many extracellular proteins. The structure of native triple helical type I collagen makes it resistant to proteolysis, and only six MMPs, MMP-1, MMP-8, MMP-13, MMP-14 (MT1-MMP), MMP-18, and MMP-2, exhibit an ability to cleave native fibrillar collagen within its triple helical domain (2-8). Similar to most MMPs, the collagenases (MMP-1, MMP-8, and MMP-13) have several structural features in common, including an N-terminal prodomain, a catalytic domain, and a short proline-rich linker connected to a hemopexin-like domain at the C terminus (9). The catalytic domain contains a Zn 2ϩ -binding site that is conserved in all MMPs and is required for catalytic activity (10, 11). The catalytic domain of the collagenases contains an additional structural Zn 2ϩ , as well as three structural Ca 2ϩ ions (12). The hemopexin-like domain contains a Ca 2ϩ and a Ca 2ϩ -Cl Ϫ ion pair (12).The three collagenases differ in patterns of tissue expression. In humans, MMP-1, which is expressed by epithelium, endothelium, fibroblasts, chondrocytes, and macrophages, seems to be the enzyme principally responsible for collagen turnover in most tissues (13-18). During cutaneous wound healing, human k...

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Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength

Cited by 569 publications

References 33 publications

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

A cellular Potts model analyzing differentiated cell behavior during in vivo vascularization of a hypoxic tissue

Structural Analysis of the α2 Integrin I Domain/Procollagenase-1 (Matrix Metalloproteinase-1) Interaction

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