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  1. Article ; Online: PI3Kγ Activates Integrin α

    Foubert, Philippe / Kaneda, Megan M / Varner, Judith A

    Cancer immunology research

    2017  Volume 5, Issue 11, Page(s) 957–968

    Abstract: Immunosuppressive myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) accumulate in tumors where they inhibit T cell-mediated antitumor immune responses and promote tumor progression. Myeloid cell PI3Kγ plays a role in ... ...

    Abstract Immunosuppressive myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) accumulate in tumors where they inhibit T cell-mediated antitumor immune responses and promote tumor progression. Myeloid cell PI3Kγ plays a role in regulating tumor immune suppression by promoting integrin α
    MeSH term(s) Animals ; Antibodies/pharmacology ; Cell Line, Tumor ; Cell Polarity/drug effects ; Cells, Cultured ; Class Ib Phosphatidylinositol 3-Kinase/antagonists & inhibitors ; Class Ib Phosphatidylinositol 3-Kinase/genetics ; Class Ib Phosphatidylinositol 3-Kinase/immunology ; Cytokines/immunology ; Female ; Immune Tolerance ; Integrin alpha4beta1/antagonists & inhibitors ; Integrin alpha4beta1/immunology ; Lymphocytes, Tumor-Infiltrating/immunology ; Macrophages/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Cells/drug effects ; Myeloid Cells/immunology ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/pathology
    Chemical Substances Antibodies ; Cytokines ; Integrin alpha4beta1 ; Class Ib Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; Pik3cg protein, mouse (EC 2.7.1.153)
    Language English
    Publishing date 2017-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-17-0143
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  2. Article ; Online: PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation

    Michael C. Schmid / Sang Won Kang / Hui Chen / Marc Paradise / Anghesom Ghebremedhin / Megan M. Kaneda / Shao-Ming Chin / Anh Do / D. Martin Watterson / Judith A. Varner

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 18

    Abstract: Myeloid cell recruitment during tumor inflammation depends on the VCAM-1 receptor integrin α4β1. Here the authors show that a high molecular weight form of myosin light chain kinase, MLCK210, is required for myeloid cell integrin α4β1 activation and ... ...

    Abstract Myeloid cell recruitment during tumor inflammation depends on the VCAM-1 receptor integrin α4β1. Here the authors show that a high molecular weight form of myosin light chain kinase, MLCK210, is required for myeloid cell integrin α4β1 activation and adhesion and that MLCK210 inhibition reduces tumor growth and inflammation in preclinical cancer models.
    Keywords Science ; Q
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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  3. Article ; Online: PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation.

    Schmid, Michael C / Kang, Sang Won / Chen, Hui / Paradise, Marc / Ghebremedhin, Anghesom / Kaneda, Megan M / Chin, Shao-Ming / Do, Anh / Watterson, D Martin / Varner, Judith A

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 1768

    Abstract: Myeloid cells play key roles in cancer immune suppression and tumor progression. In response to tumor derived factors, circulating monocytes and granulocytes extravasate into the tumor parenchyma where they stimulate angiogenesis, immune suppression and ... ...

    Abstract Myeloid cells play key roles in cancer immune suppression and tumor progression. In response to tumor derived factors, circulating monocytes and granulocytes extravasate into the tumor parenchyma where they stimulate angiogenesis, immune suppression and tumor progression. Chemokines, cytokines and interleukins stimulate PI3Kγ-mediated Rap1 activation, leading to conformational changes in integrin α4β1 that promote myeloid cell extravasation and tumor inflammation Here we show that PI3Kγ activates a high molecular weight form of myosin light chain kinase, MLCK210, that promotes myosin-dependent Rap1 GTP loading, leading to integrin α4β1 activation. Genetic or pharmacological inhibition of MLCK210 suppresses integrin α4β1 activation, as well as tumor inflammation and progression. These results demonstrate a critical role for myeloid cell MLCK210 in tumor inflammation and serve as basis for the development of alternative approaches to develop immune oncology therapeutics.
    MeSH term(s) Cell Adhesion/physiology ; Class Ib Phosphatidylinositol 3-Kinase/metabolism ; Humans ; Inflammation ; Molecular Weight ; Myeloid Cells/metabolism ; Myosin-Light-Chain Kinase/metabolism ; Neoplasms/genetics
    Chemical Substances Class Ib Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; PIK3CG protein, human (EC 2.7.1.137) ; Myosin-Light-Chain Kinase (EC 2.7.11.18)
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29471-6
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  4. Article ; Online: First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC).

    Autio, Karen A / Higano, Celestia S / Nordquist, Luke / Appleman, Leonard J / Zhang, Tian / Zhu, Xin-Hua / Babiker, Hani / Vogelzang, Nicholas J / Prasad, Sandip M / Schweizer, Michael T / Madan, Ravi A / Billotte, Stephane / Cavazos, Nora / Bogg, Orlaith / Li, Ray / Chan, Kam / Cho, Helen / Kaneda, Megan / Wang, I-Ming /
    Zheng, Jenny / Tang, Szu-Yu / Hollingsworth, Robert / Kern, Kenneth A / Petrylak, Daniel P

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 3

    Abstract: Background: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR).: Methods: For dose ... ...

    Abstract Background: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR).
    Methods: For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT). The primary endpoint was safety.
    Results: Ninety-one patients were treated in dose escalation (mCRPC=38) and expansion (BCR=35, mCRPC=18). Overall, treatment-related and immune-related adverse events occurred in 64 (70.3%) and 39 (42.9%) patients, with fatigue (40.7%), influenza-like illness (30.8%), diarrhea (23.1%), and immune-related thyroid dysfunction (19.8%) and rash (15.4%), as the most common. In patients with mCRPC, the objective response rate (ORR, 95% CI) was 5.6% (1.2% to 15.4%) and the median radiographic progression-free survival (rPFS) was 5.6 (3.5 to not estimable) months for all; the ORR was 16.7% (3.6% to 41.4%) and 6-month rPFS rate was 45.5% (24.9% to 64.1%) for those who received RP2D with measurable disease (n=18). 7.4% of patients with mCRPC achieved a ≥50% decline in baseline PSA (PSA-50), with a median duration of 4.6 (1.2-45.2) months. In patients with BCR, 9 (25.7%) achieved PSA-50; the median duration of PSA response was 3.9 (1.9-4.2) and 10.1 (6.9-28.8) months for Cohorts 5B-BCR and 1B-BCR. Overall, antigen specific T-cell response was 88.0% to PSMA, 84.0% to PSA, and 80.0% to PSCA.
    Conclusions: PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT.
    Trial registration number: NCT02616185.
    MeSH term(s) Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Docetaxel/therapeutic use ; Prostate-Specific Antigen ; Androgen Antagonists/therapeutic use ; Vaccines ; Immunotherapy ; Hormones/therapeutic use
    Chemical Substances Docetaxel (15H5577CQD) ; Prostate-Specific Antigen (EC 3.4.21.77) ; Androgen Antagonists ; Vaccines ; Hormones
    Language English
    Publishing date 2023-03-22
    Publishing country England
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2022-005702
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  5. Article ; Online: PI3Kγ inhibition suppresses microglia/TAM accumulation in glioblastoma microenvironment to promote exceptional temozolomide response.

    Li, Jie / Kaneda, Megan M / Ma, Jun / Li, Ming / Shepard, Ryan M / Patel, Kunal / Koga, Tomoyuki / Sarver, Aaron / Furnari, Frank / Xu, Beibei / Dhawan, Sanjay / Ning, Jianfang / Zhu, Hua / Wu, Anhua / You, Gan / Jiang, Tao / Venteicher, Andrew S / Rich, Jeremy N / Glass, Christopher K /
    Varner, Judith A / Chen, Clark C

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 16

    Abstract: Precision medicine in oncology leverages clinical observations of exceptional response. Toward an understanding of the molecular features that define this response, we applied an integrated, multiplatform analysis of RNA profiles derived from clinically ... ...

    Abstract Precision medicine in oncology leverages clinical observations of exceptional response. Toward an understanding of the molecular features that define this response, we applied an integrated, multiplatform analysis of RNA profiles derived from clinically annotated glioblastoma samples. This analysis suggested that specimens from exceptional responders are characterized by decreased accumulation of microglia/macrophages in the glioblastoma microenvironment. Glioblastoma-associated microglia/macrophages secreted interleukin 11 (IL11) to activate STAT3-MYC signaling in glioblastoma cells. This signaling induced stem cell states that confer enhanced tumorigenicity and resistance to the standard-of-care chemotherapy, temozolomide (TMZ). Targeting a myeloid cell restricted an isoform of phosphoinositide-3-kinase, phosphoinositide-3-kinase gamma isoform (PI3Kγ), by pharmacologic inhibition or genetic inactivation disrupted this signaling axis by reducing microglia/macrophage-associated IL11 secretion in the tumor microenvironment. Mirroring the clinical outcomes of exceptional responders, PI3Kγ inhibition synergistically enhanced the anti-neoplastic effects of TMZ in orthotopic murine glioblastoma models. Moreover, inhibition or genetic inactivation of PI3Kγ in murine glioblastoma models recapitulated expression profiles observed in clinical specimens isolated from exceptional responders. Our results suggest key contributions from tumor-associated microglia/macrophages in exceptional responses and highlight the translational potential for PI3Kγ inhibition as a glioblastoma therapy.
    MeSH term(s) Adult ; Animals ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Class Ib Phosphatidylinositol 3-Kinase/metabolism ; Drug Resistance, Neoplasm/physiology ; Female ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Interleukin-11/immunology ; Interleukin-11/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Nude ; Microglia/metabolism ; Microglia/physiology ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Signal Transduction/drug effects ; Temozolomide/metabolism ; Temozolomide/pharmacology ; Tumor Microenvironment/drug effects ; Tumor-Associated Macrophages/metabolism ; Tumor-Associated Macrophages/physiology ; Mice
    Chemical Substances Interleukin-11 ; Phosphoinositide-3 Kinase Inhibitors ; Class Ib Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; PIK3CG protein, human (EC 2.7.1.137) ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; Temozolomide (YF1K15M17Y)
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2009290118
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    Zs.A 1148: Show issues Location:
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  6. Article ; Online: Integrin CD11b activation drives anti-tumor innate immunity.

    Schmid, Michael C / Khan, Samia Q / Kaneda, Megan M / Pathria, Paulina / Shepard, Ryan / Louis, Tiani L / Anand, Sudarshan / Woo, Gyunghwi / Leem, Chris / Faridi, M Hafeez / Geraghty, Terese / Rajagopalan, Anugraha / Gupta, Seema / Ahmed, Mansoor / Vazquez-Padron, Roberto I / Cheresh, David A / Gupta, Vineet / Varner, Judith A

    Nature communications

    2018  Volume 9, Issue 1, Page(s) 5379

    Abstract: Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes ... ...

    Abstract Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes integrin CD11b. Here we report that, unexpectedly, integrin CD11b does not regulate myeloid cell recruitment to tumors but instead controls myeloid cell polarization and tumor growth. CD11b activation promotes pro-inflammatory macrophage polarization by stimulating expression of microRNA Let7a. In contrast, inhibition of CD11b prevents Let7a expression and induces cMyc expression, leading to immune suppressive macrophage polarization, vascular maturation, and accelerated tumor growth. Pharmacological activation of CD11b with a small molecule agonist, Leukadherin 1 (LA1), promotes pro-inflammatory macrophage polarization and suppresses tumor growth in animal models of murine and human cancer. These studies identify CD11b as negative regulator of immune suppression and a target for cancer immune therapy.
    MeSH term(s) Animals ; Benzoates/pharmacology ; Benzoates/therapeutic use ; CD11b Antigen/agonists ; CD11b Antigen/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; Melanoma, Experimental/drug therapy ; Melanoma, Experimental/immunology ; Mice, Transgenic ; MicroRNAs/metabolism ; Neovascularization, Pathologic ; Proto-Oncogene Proteins c-myc/metabolism ; Thiohydantoins/pharmacology ; Thiohydantoins/therapeutic use
    Chemical Substances Benzoates ; CD11b Antigen ; MicroRNAs ; Myc protein, mouse ; Proto-Oncogene Proteins c-myc ; Thiohydantoins ; leukadherin-1 ; mirnlet7 microRNA, mouse
    Language English
    Publishing date 2018-12-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-018-07387-4
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  7. Article ; Online: Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics.

    Kaneda, Megan M / Caruthers, Shelton / Lanza, Gregory M / Wickline, Samuel A

    Annals of biomedical engineering

    2009  Volume 37, Issue 10, Page(s) 1922–1933

    Abstract: A broad array of nanomaterials is available for use as contrast agents for molecular imaging and drug delivery. Due to the lack of endogenous background signal in vivo and the high NMR sensitivity of the (19)F atom, liquid perfluorocarbon nanoemulsions ... ...

    Abstract A broad array of nanomaterials is available for use as contrast agents for molecular imaging and drug delivery. Due to the lack of endogenous background signal in vivo and the high NMR sensitivity of the (19)F atom, liquid perfluorocarbon nanoemulsions make ideal agents for cellular and magnetic resonance molecular imaging. The perfluorocarbon core material is surrounded by a lipid monolayer which can be functionalized with a variety of agents including targeting ligands, imaging agents and drugs either individually or in combination. Multiple copies of targeting ligands (approximately 20-40 monoclonal antibodies or 200-400 small molecule ligands) serve to enhance avidity through multivalent interactions while the composition of the particle's perfluorocarbon core results in high local concentrations of (19)F. Additionally, lipophilic drugs contained within molecularly targeted nanoemulsions can result in contact facilitated drug delivery to target cells. Ultimately, the dual use of perfluorocarbon nanoparticles for both site targeted drug delivery and molecular imaging may provide both imaging of disease states as well as conclusive evidence that drug delivery is localized to the area of interest. This review will focus on liquid perfluorocarbon nanoparticles as (19)F molecular imaging agents and for targeted drug delivery in cancer and cardiovascular disease.
    MeSH term(s) Contrast Media ; Diagnostic Imaging/trends ; Drug Delivery Systems/trends ; Emulsions/chemistry ; Fluorocarbons/chemistry ; Fluorocarbons/therapeutic use ; Image Enhancement/methods ; Molecular Probe Techniques/trends ; Nanoparticles/chemistry ; Nanoparticles/therapeutic use
    Chemical Substances Contrast Media ; Emulsions ; Fluorocarbons
    Language English
    Publishing date 2009-01-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 185984-5
    ISSN 1573-9686 ; 0191-5649 ; 0090-6964
    ISSN (online) 1573-9686
    ISSN 0191-5649 ; 0090-6964
    DOI 10.1007/s10439-009-9643-z
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1018: Show issues Location:
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  8. Article ; Online: 19F MRS assessment of siRNA delivery to vascular cells via perfluorocarbon nanoparticles

    Wickline Samuel A / Lanza Gregory M / Kaneda Megan M / Myerson Jacob W

    Journal of Cardiovascular Magnetic Resonance, Vol 12, Iss Suppl 1, p P

    2010  Volume 103

    Keywords Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Cardiovascular ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
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  9. Article ; Online: Mechanisms of nucleotide trafficking during siRNA delivery to endothelial cells using perfluorocarbon nanoemulsions.

    Kaneda, Megan M / Sasaki, Yo / Lanza, Gregory M / Milbrandt, Jeffrey / Wickline, Samuel A

    Biomaterials

    2010  Volume 31, Issue 11, Page(s) 3079–3086

    Abstract: RNA interference (RNAi) is a useful in vitro research tool, but its application as a safe and effective therapeutic agent may benefit from improved understanding of mechanisms of exogenous siRNA delivery, including cell trafficking and sorting patterns. ... ...

    Abstract RNA interference (RNAi) is a useful in vitro research tool, but its application as a safe and effective therapeutic agent may benefit from improved understanding of mechanisms of exogenous siRNA delivery, including cell trafficking and sorting patterns. We report the development of a transfection reagent for siRNA delivery which employs a distinctive non-digestive mode of particle-cell membrane interaction through the formation of a hemifusion complex resulting in lipid raft transport of cargo to the cytosol, bypassing the usual endosomal nanoparticle uptake pathway. We further demonstrate markedly enhanced efficacy over conventional transfection agents for suppressing endothelial cell expression of upregulated vascular adhesion molecules.
    MeSH term(s) Animals ; Cations/chemistry ; Cell Line ; Cell Membrane Structures/metabolism ; Drug Carriers/chemistry ; Drug Carriers/metabolism ; Emulsions/chemistry ; Endothelial Cells/metabolism ; Fluorocarbons/chemistry ; Indicators and Reagents/metabolism ; Lipids/chemistry ; Mice ; Nanoparticles/chemistry ; Nucleotides/genetics ; Nucleotides/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Transfection/methods
    Chemical Substances Cations ; Drug Carriers ; Emulsions ; Fluorocarbons ; Indicators and Reagents ; Lipids ; Lipofectamine ; Nucleotides ; RNA, Small Interfering
    Language English
    Publishing date 2010-01-25
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2010.01.006
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  10. Article ; Online: Endothelial cell migration in human plasma is enhanced by a narrow range of added sphingosine 1-phosphate: implications for biomaterials design.

    Alford, Shannon K / Kaneda, Megan M / Wacker, Bradley K / Elbert, Donald L

    Journal of biomedical materials research. Part A

    2008  Volume 88, Issue 1, Page(s) 205–212

    Abstract: Sphingosine 1-phosphate (S1P) promotes endothelial cell migration in vitro and may potentially impact the endothelialization of implanted biomaterials. However, the effects of S1P on endothelial cells (EC) in flowing blood could be negligible due to ... ...

    Abstract Sphingosine 1-phosphate (S1P) promotes endothelial cell migration in vitro and may potentially impact the endothelialization of implanted biomaterials. However, the effects of S1P on endothelial cells (EC) in flowing blood could be negligible due to preactivation of signaling cascades. We previously developed biomaterials that release S1P and wished to determine through in vitro experiments the extent to which EC respond to S1P added to human platelet poor plasma. We found that addition of 200 nM S1P to platelet poor plasma significantly increased cell migration in two migration models. A lower concentration of S1P added to plasma (100 nM) did not increase endothelial cell migration rates, while the cell migration response was saturated above 200 nM S1P. Expression of the main S1P receptor in EC, S1P(1), was elevated in plasma compared to low serum medium, but addition of VEGF or fluid flow elicited a further increase in S1P(1) mRNA, consistent with the synergistic effects observed between S1P, VEGF, and fluid flow. Thus, sustained delivery of S1P from biomaterials might only enhance endothelial cell migration if the concentration of S1P at the surface of the material stimulated adjacent EC to the same extent as approximately 200 nM S1P added to plasma.
    MeSH term(s) Biocompatible Materials/therapeutic use ; Blood Circulation ; Cell Movement/drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drug Synergism ; Endothelial Cells/physiology ; Humans ; Lysophospholipids/pharmacology ; Models, Biological ; Receptors, Lysosphingolipid/biosynthesis ; Sphingosine/analogs & derivatives ; Sphingosine/pharmacology ; Up-Regulation/drug effects ; Vascular Endothelial Growth Factor A/pharmacology
    Chemical Substances Biocompatible Materials ; Lysophospholipids ; Receptors, Lysosphingolipid ; Vascular Endothelial Growth Factor A ; sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42)
    Language English
    Publishing date 2008-02-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2099989-6
    ISSN 1552-4965 ; 1549-3296 ; 0021-9304
    ISSN (online) 1552-4965
    ISSN 1549-3296 ; 0021-9304
    DOI 10.1002/jbm.a.31885
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