Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone

Leblanc, Raphaël; Lee, Sue-Chin; David, Marion; Bordet, Jean‐Claude; Norman, Dean C.; Patil, Renukadevi; Miller, Duane D.; Sahay, Debashish; Ribeiro, J. L.; Clézardin, Philippe; Tigyi, Gábor; Peyruchaud, Olivier

doi:10.1182/blood-2014-04-568683

Cited by 148 publications

(145 citation statements)

References 40 publications

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“…Then, released ATP binds to the endothelial purinergic P2Y2 receptor, stimulating cancer cell intravasation and metastatic dissemination to the lung, thus demonstrating that ATP secreted from platelets supports platelet-induced tumor cell transendothelial migration and metastatic dissemination 37 ( Figure 1). Coincubation of platelets with metastatic breast cancer cells under both steering 38 and passive 39 conditions mediate lysophosphatidic acid (LPA) production that subsequently activates tumor LPA 1 receptor promoting cell invasion via a PI3K/zinc finger E-box-binding homeobox 1/microRNA-21-dependent signaling pathway. 40 The physical interaction between platelets and tumor cells is a wellknown prerequisite for platelet prometastatic activity mediating secretion of protumoral factors.…”

Section: Platelets and Ctc Invasion/extravasationmentioning

confidence: 99%

“…24 Released PDGF can activate Notch1 and STAT1 signaling pathways, inducing and/or maintaining EMT on CTCs. 25,26 Direct interaction of platelet membranes exposes active P-selectin and GPIIb-IIIa, 41 and the secretion of LPA by activated platelets supports CTC invasion 39,40 and ATP promotes transendothelial cell migration. 37 Figure was generated using the database of images from Servier Medical Art from Servier (http://creativecommons.org/licenses/by/3.0/fr/).…”

Section: Platelets and Ctc Invasion/extravasationmentioning

confidence: 99%

“…55 We demonstrated that circulating nontumoral ATX can be stored in a-granules of resting platelets and released on breast cancer cell stimulation. 39 In vitro cell adhesion and proliferation assays indicated that exogenous ATX could bind both tumor a V b 3 and platelet a IIb b 3 integrins. 39,56,57 Such a physical interaction between ATX and b 3 integrins might promote local production of LPA, which in turn could act more efficiently on cancer cells, stimulating metastasis and cancer dissemination to the bone 39 ( Figure 2).…”

Section: Platelets and Bone Metastasismentioning

confidence: 99%

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Metastasis: new functional implications of platelets and megakaryocytes

Leblanc

Peyruchaud

2016

Blood

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183

131

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Platelets are essential components of hemostasis. Due to a plethora of factors released on activation, platelet functions are also connected to tumor growth, notably by acting on angiogenesis. It is now well recognized that major roles of platelets in the poor outcome of cancer patients occurs during hematogenous dissemination of cancer cells. In this review, we describe recent insights into the molecular mechanisms supporting the prometastatic activity of platelets. Platelets have been shown to promote survival of circulating tumor cells (CTCs) in the bloodstream by conferring resistance to the shear stress and attack from natural killer cells. Recently, platelets were found to promote and/or maintain the state of epithelial to mesenchymal transition on CTCs through platelet secretion of transforming growth factor β in response to CTC activation. At a later stage in the metastatic process, platelets promote extravasation and establishment of metastatic cells in distant organs as observed in bone. This particular environment is also the site of hematopoiesis, megakaryocytopoiesis, and platelet production. Increasing the number of megakaryocytes (MKs) in the bone marrow results in a high bone mass phenotype and inhibits skeletal metastasis formation of prostate cancer cells. As a result of their specific location in vascular niches in the bone marrow, MK activity might contribute to the “seed and soil” suitability between CTCs and bone. In conclusion, recent findings have made a great advance in our knowledge on how platelets contribute to the metastatic dissemination of cancer cells and that may support the development of new antimetastasis therapies.

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Section: Platelets and Ctc Invasion/extravasationmentioning

confidence: 99%

Section: Platelets and Ctc Invasion/extravasationmentioning

confidence: 99%

Section: Platelets and Bone Metastasismentioning

confidence: 99%

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Metastasis: new functional implications of platelets and megakaryocytes

Leblanc

Peyruchaud

2016

Blood

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183

131

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“…A number of studies have demonstrated that ATX activity promotes in vitro motogenic activity in ovarian ( 119,147 ), hepatocellular ( 148 ), breast, and melanoma cell lines ( 118 ), among others, while pharmacological and genetic inhibition of ATX decreases lung metastasis in a murine orthotopic model of breast cancer ( 103,149 ). Available evidence suggests that metastasis to bone can be promoted by ATX through multiple mechanisms, including regulation of osteoclast differentiation ( 103 ), interaction with integrin ␣ V ␤ 3 expressed on the surface of tumor cells ( 150 ), and bone resorption through the induction of IL6 and IL8 expression ( 151 ).…”

Section: Role In Physiology and Cancer Pathophysiologymentioning

confidence: 99%

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

Federico

Jeong

Vellano

et al. 2016

Journal of Lipid Research

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a 125 kDa glycoprotein composed of 915 amino acids ( 1 ). Because it promoted chemotaxis on melanoma cells in an autocrine fashion, the protein was aptly named auto-taxin. Four years after the discovery of the fi rst variant, now commonly referred to as ATX ␣ , or melanoma ATX, a second isoform was cloned by the same team from the teratocarcinoma cell line, Ntera2D1. This polypeptide shared 94% identity with the melanoma protein and was immediately recognized as the alternatively spliced product of the same gene ( 2 ).The initial characterization of the fi rst isoform revealed that ATX biological activity was sensitive to pertussis toxin treatment. Furthermore, not only did the polypeptide share close homology with the murine pyrophosphatase/ type I phosphodiesterase (PDE) PC-1, including a threonine residue crucial for PDE enzymatic activity, but it was also able to hydrolyze PDE substrates in vitro ( 3 ). The confi rmation that ATX was an enzyme came when a new PDE, the PDE1/nucleotide pyrophosphatase (PD-1 ␣ /PDNP 2), was cloned from a cDNA library of human retina and found to be identical to the sequence of melanoma ATX ␣ with the exception of a missing stretch of 52 amino acids encoded by exon 12 in the central region of the open reading frame. The transcript of this variant, now frequently referred to as ATX ␤ , or teratoma ATX, produced a 863 amino acid polypeptide chain with a mass of 99,034 Da ( 4 ), and was independently isolated a few years later in mouse tissues ( 5 ). The third ATX isoform was detected for the fi rst time in rat brain, but was originally designated as PD-I ␣ , a brain-specifi c PDE I/nucleotide pyrophosphatase ( 6 ). Further research showed that PD-I ␣ was identical to ATX ␤ teratoma protein, except for the presence of an additional stretch of 25 amino acids encoded by an alternatively Abstract The ectonucleotide pyrophosphatase/phosphodiesterase type 2, more commonly known as autotaxin (ATX), is an ecto-lysophospholipase D encoded by the human ENNP2 gene. ATX is expressed in multiple tissues and participates in numerous key physiologic and pathologic processes, including neural development, obesity, infl ammation, and oncogenesis, through the generation of the bioactive lipid, lysophosphatidic acid. Overwhelming evidence indicates that altered ATX activity leads to oncogenesis and cancer progression through the modulation of multiple hallmarks of cancer pathobiology. Here, we review the structural and catalytic characteristics of the ectoenzyme, how its expression and maturation processes are regulated, and how the systemic integration of its pleomorphic effects on cells and tissues may contribute to cancer initiation, progression, and therapy. Additionally, the up-to-date spectrum of the most frequent ATX genomic alterations from The Cancer Genome Atlas project is reported for a subset of cancers. ( Fig. 1 ). In 1992, the fi rst alternatively spliced isoform was cloned from the melanoma cell line, A2058, and characterized as STRUCTURE AND ENZYMATIC ACTIVITY ATX belongs to the nuc...

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“…Furthermore, studies from different teams suggested that platelet-derived ATX also could control metastasis of breast cancer cells to bone, similar to tumor-derived ATX. 84 It has been a consensus that the classic LPARs (LPAR1-3) were involved in tumor angiogenesis, migration, invasion, and metastasis. 67,77,82,85,86 The mechanisms include induction of VEGF expression, 67 promotion of uPA expression, 86 and activation of Ras/Raf-MAPK, G12/13-RhoRhoA, PI3K-AKT/PKB, 87 beta-arrestin/Ral, 82 Gq11/p38, 85 PKC/alpha-CARMA3, 86 and EGFR 78 signaling pathways.…”

Section: Expression Of Atx/lpa Axis In Cancermentioning

confidence: 99%

The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer

et al. 2017

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Autotaxin, an ecto-lysophospholipase D encoded by the human ENNP2 gene, is expressed in multiple tissues, and participates in numerous critical physiologic and pathologic processes including inflammation, pain, obesity, embryo development, and cancer via the generation of the bioactive lipid lysophosphatidate. Overwhelming evidences indicate that the autotaxin/lysophosphatidate signaling axis serves key roles in the numerous processes central to tumorigenesis and progression, including proliferation, survival, migration, invasion, metastasis, cancer stem cell, tumor microenvironment, and treatment resistance by interacting with a series of at least six G-protein-coupled receptors (LPAR1-6). This review provides an overview of the autotaxin/lysophosphatidate axis and collates current knowledge regarding its specific role in pancreatic cancer. With a deeper understanding of the critical role of the autotaxin/lysophosphatidate axis in pancreatic cancer, targeting autotaxin or lysophosphatidate receptor may be a potential and promising strategy for cancer therapy.

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Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone

Cited by 148 publications

References 40 publications

Metastasis: new functional implications of platelets and megakaryocytes

Metastasis: new functional implications of platelets and megakaryocytes

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer

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