Dual role of pericyte α6β1-integrin in tumour blood vessels

Reynolds, Louise E.; D’Amico, Gabriela; Lechertier, Tanguy; Papachristodoulou, Alexandros; Muñoz‐Félix, José M.; Arcangelis, Adèle De; Baker, Marianne; Serrels, Bryan; Hodivala‐Dilke, Kairbaan

doi:10.1242/jcs.197848

Cited by 28 publications

(27 citation statements)

References 55 publications

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“…Consistent with these data, integrin‐α1∼α3 and ‐α6 are found in cultured CNS pericytes at mRNA level (Stratman et al ., ). At protein level, expression of integrin‐α2 (Yao et al ., ), ‐α6 (Reynolds et al ., ), and ‐β1 (Abraham et al ., ; Turlo et al ., ) in pericytes/SMCs has been reported. In addition, there is also evidence showing that pericytes synthesize integrin‐α7 (Flintoff‐Dye et al ., ; Silva et al ., ).…”

Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

Laminins and their receptors in the CNS

Nirwane

Yao

2018

Biological Reviews

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Laminin, an extracellular matrix protein, is widely expressed in the central nervous system (CNS). By interacting with integrin and non-integrin receptors, laminin exerts a large variety of important functions in the CNS in both physiological and pathological conditions. Due to the existence of many laminin isoforms and their differential expression in various cell types in the CNS, the exact functions of each individual laminin molecule in CNS development and homeostasis remain largely unclear. In this review, we first briefly introduce the structure and biochemistry of laminins and their receptors. Next, the dynamic expression of laminins and their receptors in the CNS during both development and in adulthood is summarized in a cell-type-specific manner, which allows appreciation of their functional redundancy/compensation. Furthermore, we discuss the biological functions of laminins and their receptors in CNS development, blood-brain barrier (BBB) maintenance, neurodegeneration, stroke, and neuroinflammation. Last, key challenges and potential future research directions are summarized and discussed. Our goals are to provide a synthetic review to stimulate future studies and promote the formation of new ideas/hypotheses and new lines of research in this field.

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Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

Laminins and their receptors in the CNS

Nirwane

Yao

2018

Biological Reviews

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“…During development, pericytes are first attracted to newly formed capillaries via the endothelial-secreted chemoattractant platelet-derived growth factor (PDGF)-BB, which binds to PDGF receptor β (PDGFRβ) on pericytes (Lindahl et al, 1997;Benjamin et al, 1998). Integrin-mediated adhesion of pericytes to laminin helps to maintain expression of PDGFRβ (Durbeej, 2010;Reynolds et al, 2017). Interference with PDGF-BB/PDGFRβ signaling is sufficient to disrupt endothelial-pericyte interactions (Lindahl et al, 1997), indicating that perpetual signaling through PDGFRβ is critical to maintain pericyte localization to capillary endothelial cells.…”

Section: Introduction: What Is a Pericyte?mentioning

confidence: 99%

Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications

Nwadozi

Rudnicki

Haas

2020

Front. Cell Dev. Biol.

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Pericytes are mural vascular cells found predominantly on the abluminal wall of capillaries, where they contribute to the maintenance of capillary structural integrity and vascular permeability. Generally quiescent cells in the adult, pericyte activation and proliferation occur during both physiological and pathological vascular and tissue remodeling. A considerable body of research indicates that pericytes possess attributes of a multipotent adult stem cell, as they are capable of self-renewal as well as commitment and differentiation into multiple lineages. However, pericytes also display phenotypic heterogeneity and recent studies indicate that lineage potential differs between pericyte subpopulations. While numerous microenvironmental cues and cell signaling pathways are known to regulate pericyte functions, the roles that metabolic pathways play in pericyte quiescence, self-renewal or differentiation have been given limited consideration to date. This review will summarize existing data regarding pericyte metabolism and will discuss the coupling of signal pathways to shifts in metabolic pathway preferences that ultimately regulate pericyte quiescence, self-renewal and trans-differentiation. The association between dysregulated metabolic processes and development of pericyte pathologies will be highlighted. Despite ongoing debate regarding pericyte classification and their functional capacity for trans-differentiation in vivo, pericytes are increasingly exploited as a cell therapy tool to promote tissue healing and regeneration. Ultimately, the efficacy of therapeutic approaches hinges on the capacity to effectively control/optimize the fate of the implanted pericytes. Thus, we will identify knowledge gaps that need to be addressed to more effectively harness the opportunity for therapeutic manipulation of pericytes to control pathological outcomes in tissue remodeling.

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“…Integrins are known to regulate cell-cell and cell-matrix interactions and it has amply been reported that integrins may be involved in tumor progression and metastasis [39][40][41]. According to the "seed-and-soil" hypothesis, metastatic organotropism is one of the characteristics of cancer [42].…”

Section: Discussionmentioning

confidence: 99%

The exosomal integrin α5β1/AEP complex derived from epithelial ovarian cancer cells promotes peritoneal metastasis through regulating mesothelial cell proliferation and migration

Tang

Zhu

et al. 2020

Cell Oncol.

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Purpose Epithelial ovarian cancer (EOC) is one of the most malignant cancers in the gynecologic system. Many patients are diagnosed at an advanced stage with disseminated intra-peritoneal metastases. EOC spreads via both direct extension and transcoelomic spread. However, the interplay between human peritoneal mesothelial cells (HPMCs) and EOC cells is still ambiguous. We hypothesize that integrins (ITG) in HPMCs may play important roles in EOC metastasis. Methods The expression of different integrin subtypes from HPMCs was assessed using Western blotting. The expression of integrin α5β1 (ITGA5B1) and its co-localization with asparaginyl endopeptidase (AEP) in HPMCs derived from EOC patients (EOC-HPMCs) were assessed using immunofluorescence. The role and mechanism of the exosomal ITGA5B1/AEP complex in HPMCs was assessed using both in vitro and in vivo assays. A retrospective study involving 234 cases was carried out to assess ITGA5B1 and AEP levels in circulating sera and ascites of EOC patients, as well as associations between ITGA5B1/AEP expression and overall survival. Results We found that ITGA5B1was highly expressed and co-localized with AEP in EOC cells, and that the exosomal ITGA5B1/AEP complex secreted by EOC cells played an important role in the proliferation and migration of HPMCs. High levels of exosomal ITGA5B1/AEP were also found in circulating sera and ascites of EOC patients, and the expression of ITGA5B1/AEP in EOC tissues was found to be negatively associated with overall survival. Conclusions Our data indicate that EOCs may regulate the function of HPMCs through exosomal ITGA5B1/AEP, which may be crucial for peritoneal metastasis.

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Dual role of pericyte α6β1-integrin in tumour blood vessels

Cited by 28 publications

References 55 publications

Laminins and their receptors in the CNS

Laminins and their receptors in the CNS

Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications

The exosomal integrin α5β1/AEP complex derived from epithelial ovarian cancer cells promotes peritoneal metastasis through regulating mesothelial cell proliferation and migration

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