Visualization of CD146 dimerization and its regulation in living cells

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 05/2007; 1773(4):513-20. DOI: 10.1016/j.bbamcr.2007.01.009
Source: PubMed


This article is about resettled Afghan Hazaras in Australia, many of whom are currently undergoing a complex process of transition (from transience into a more stable position) for the first time in their lives. Despite their permanent residency status, we show how resettlement can
be a challenging transitional experience. For these new migrants, we argue that developing a sense of belonging during the transition period is a critical rite of passage in the context of their political and cultural identity. A study of forced migrants such as these, moving out of one transient
experience into another transitional period (albeit one that holds greater promise and permanence) poses a unique intellectual challenge. New understandings about the ongoing, unpredictable consequences of ‘transience’ for refugee communities is crucial as we discover what might
be necessary, as social support structures, to facilitate the process of transition into a distinctly new environment. The article is based on a doctoral ethnographic study of 30 resettled Afghan Hazara living in the region of Dandenong in Melbourne, Australia. Here, we include four of these
participants’ reflections of transition during different phases of their resettlement. These reflections were particularly revealing of the ways in which some migrants deal with change and acquire a sense of belonging to the community. Taking a historical view, and drawing on Bourdieu’s
notion of symbolic social capital to highlight themes in individual experiences of belonging, we show how some new migrants adjust and learn to ‘embody’ their place in the new country. Symbolic social capital illuminates how people access and use resources such as social networks
as tools of empowerment, reflecting how Hazara post-arrival experiences are tied to complex power relations in their everyday social interactions and in their life trajectories as people in transition. We learned that such tools can facilitate the formation of Hazara migrant identities and
are closely tied to their civic community participation, English language development, and orientation in, as well as comprehension of local cultural knowledge and place. This kind of theorization allows refugee, post-refugee and recent migrant narratives to be viewed not merely as static
expressions of loss, trauma or damage, but rather as individual experiences of survival, adaptation and upward mobility.


Available from: Xun Shen, Jan 23, 2014
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    • "This transmembrane glycoprotein has important functions in early and late development and it has been suggested to play an important role in cancer, angiogenesis, cardiovascular diseases and placentation [30]. Moreover, a significant number of studies in the field of cancer research have assigned to CD146 a critical role in tumor growth and metastasis, as well as in tumor angiogenesis [31], [32]. At the core of an efficient cross-talk between endothelial cells, mural cells and ECM, are thought to be a diversity of proteins, namely PDGF, TGF, VEGF, Collagen, laminin and others, both soluble or trapped on the ECM [33]–[35]. "
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    ABSTRACT: In recent years several studies have been supporting the existence of a close relationship in terms of function and progeny between Mesenchymal Stem Cells (MSCs) and Pericytes. This concept has opened new perspectives for the application of MSCs in Tissue Engineering (TE), with special interest for the pre-vascularization of cell dense constructs. In this work, cell sheet technology was used to create a scaffold-free construct composed of osteogenic, endothelial and perivascular-like (CD146(+)) cells for improved in vivo vessel formation, maturation and stability. The CD146 pericyte-associated phenotype was induced from human bone marrow mesenchymal stem cells (hBMSCs) by the supplementation of standard culture medium with TGF-β1. Co-cultured cell sheets were obtained by culturing perivascular-like (CD146(+)) cells and human umbilical vein endothelial cells (HUVECs) on an hBMSCs monolayer maintained in osteogenic medium for 7 days. The perivascular-like (CD146(+)) cells and the HUVECs migrated and organized over the collagen-rich osteogenic cell sheet, suggesting the existence of cross-talk involving the co-cultured cell types. Furthermore the presence of that particular ECM produced by the osteoblastic cells was shown to be the key regulator for the singular observed organization. The osteogenic and angiogenic character of the proposed constructs was assessed in vivo. Immunohistochemistry analysis of the explants revealed the integration of HUVECs with the host vasculature as well as the osteogenic potential of the created construct, by the expression of osteocalcin. Additionally, the analysis of the diameter of human CD146 positive blood vessels showed a higher mean vessel diameter for the co-cultured cell sheet condition, reinforcing the advantage of the proposed model regarding blood vessels maturation and stability and for the in vitro pre-vascularization of TE constructs.
    PLoS ONE 07/2012; 7(7):e41051. DOI:10.1371/journal.pone.0041051 · 3.23 Impact Factor
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    • "Results CD146 dimerization is required for VEGF-induced tube formation and signal transduction Our group has previously found that CD146 dimerization in endothelial cells is inducible and regulatable by the NF-κB pathway in tumor-induced angiogenesis [16]. To study tumor-induced angiogenesis , VEGF, an important tumor-secreted cytokine, was used to stimulate human endothelial cells. "
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    ABSTRACT: CD146 dimerization plays an important role in tumor-induced angiogenesis. Stimulation of target cells with vascular endothelial growth factor (VEGF), a major angiogenic factor produced by tumor cells, elicits a burst of reactive oxygen species (ROS) that enhances angiogenesis. However, the molecular mechanism coupling CD146 dimerization with the VEGF-related oxidant-generating apparatus has not been elucidated. Here, we show that CD146 dimerization is induced by VEGF and is significantly diminished by pretreatment with diphenylene iodonium, an inhibitor of NADPH oxidase, suggesting a potential role for NADPH oxidase (NOX) in VEGF-induced CD146 dimerization. Importantly, we found that overexpression of NADPH oxidase 4 (NOX4), which is the predominant NOX expressed in endothelial cells, significantly enhances VEGF-induced ROS generation and CD146 dimerization. By contrast, these VEGF effects were dramatically attenuated after transfection with siRNA to reduce NOX4 expression. Furthermore, expression of Rac1 N17, a dominant negative mutant of Rac1, a member of the Rho family of small GTPases, suppressed VEGF-induced ROS generation and CD146 dimerization. These studies show for the first time that VEGF alteration of CD146 dimerization is mediated via a NOX4-dependent pathway and provide novel insight into the significant role of NOX in redox regulation of the dimerization of cell adhesion molecules.
    Free Radical Biology and Medicine 07/2010; 49(2):227-36. DOI:10.1016/j.freeradbiomed.2010.04.007 · 5.74 Impact Factor
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    • "Previously, we have reported the dimerization of CD146 in living cells using the method of FRET (Bu et al., 2007). We postulated that dimerization may be related to the role of CD146 in tumor angiogenesis . "
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    ABSTRACT: Tumor angiogenesis, induced by tumor-secreted pro-angiogenic factors, is an essential process for cancer development and metastasis. CD146 is identified as an endothelial cell adhesion molecule and implicated in blood vessel formation, however, its exact role in angiogenesis, particularly tumor angiogenesis, and its potential function of mediating downstream signaling are still unclear. In present study, we evidenced that silencing endogenous endothelial CD146 by RNAi significantly impaired hepatocarcinoma cell secretions-promoted tubular morphogenesis and -enhanced motility of endothelial cells. Biochemical studies revealed that CD146 was required for the activation of p38/IKK/NF kappaB signaling cascade and up-regulation of NF kappaB downstream pro-angiogenic genes, notably IL-8, ICAM-1 and MMP9, in response to tumor secretions. Interestingly, specific anti-CD146 mAb AA98, which bound a conformational epitope depending on C452-C499 disulfide bond, could abrogate NF kappaB activation and tumor angiogenesis, whereas another anti-CD146 mAb AA1 recognizing a linear epitope containing aa50-54 did not have such effects. Further structure-function analysis identified that C452-C499 disulfide bond within the fifth extracellular Ig domain was indispensible for CD146-mediated signaling and tube formation. Moreover, dimerization of CD146, which was enhanced by tumor secretions and suppressed by AA98 but not AA1, also relied on C452 and C499. Together, this study for the first time uncovered the pro-angiogenic role of CD146 and also pinpointed the key structural basis responsible for its signaling function and dimerization. These findings also suggested that CD146 might serve as not just a cell adhesion molecule but also a membrane signal receptor in tumor-induced angiogenesis.
    The international journal of biochemistry & cell biology 11/2009; 41(11):2163-72. DOI:10.1016/j.biocel.2009.03.014 · 4.05 Impact Factor
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