The Role of Platelet Cell Surface P-Selectin for the Direct Platelet-Tumor Cell Contact During Metastasis Formation in Human Tumors

Mammalian platelets, devoid of nuclei, are the smallest cells in the blood stream. They are essential for hemostasis, but also transmit cell signals that are necessary for regenerative and generative processes such as inflammation, immunity and tissue repair. In particular, in malignancies they are also associated with cell proliferation, angiogenesis, and epithelial-mesenchymal transition. Platelets promote metastasis and resistance to anti-tumor treatment. However, fundamental principles of the interaction between them and target cells within tumors are complex and still quite obscure. When injected into animals or circulating in the blood of cancer patients, cancer cells ligate platelets in a timely manner closely related to platelet activation either by direct contact or by cell-derived substances or microvesicles. In this context, a large number of different surface molecules and transduction mechanisms have been identified, although the results are sometimes species-specific and not always valid to humans. In this mini-review, we briefly summarize the current knowledge on the role of the direct and indirect platelet-tumor interaction for single steps of the metastatic cascade and specifically focus on the functional role of P-selectin.

[1]  D. Ichikawa,et al.  Platelets enhance malignant behaviours of gastric cancer cells via direct contacts , 2020, British Journal of Cancer.

[2]  R. Muschel,et al.  Platelets and Metastasis: New Implications of an Old Interplay , 2020, Frontiers in Oncology.

[3]  C. Heldin,et al.  Platelet-Specific PDGFB Ablation Impairs Tumor Vessel Integrity and Promotes Metastasis , 2020, Cancer Research.

[4]  J. Kinoshita,et al.  Extravasated platelet aggregation contributes to tumor progression via the accumulation of myeloid-derived suppressor cells in gastric cancer with peritoneal metastasis , 2020, Oncology letters.

[5]  L. Borsig,et al.  Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction , 2020, Cancers.

[6]  T. Lange,et al.  Systematic analysis of the human tumor cell binding to human vs. murine E- and P-selectin under static vs. dynamic conditions , 2020, Glycobiology.

[7]  P. Jayaraman,et al.  Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX , 2020, Oncogenesis.

[8]  Wu-Hu Zhang,et al.  Tumor-infiltrating platelets predict postoperative recurrence and survival in resectable pancreatic neuroendocrine tumor , 2019, World journal of gastroenterology.

[9]  Cynthia A. Reinhart-King,et al.  Engineered models to parse apart the metastatic cascade , 2019, npj Precision Oncology.

[10]  K. Bieback,et al.  Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: A joint publication from the AABB and the International Society of Cell Therapy. , 2019, Cytotherapy.

[11]  J. Mitchell,et al.  Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2 , 2019, The Journal of clinical investigation.

[12]  M. Falasca,et al.  The History of Armand Trousseau and Cancer-Associated Thrombosis , 2019, Cancers.

[13]  U. Schumacher,et al.  The functional role of integrins during intra- and extravasation within the metastatic cascade , 2019, Molecular Cancer.

[14]  K. Pantel,et al.  Autologous cell lines from circulating colon cancer cells captured from sequential liquid biopsies as model to study therapy-driven tumor changes , 2018, Scientific Reports.

[15]  M. Schlesinger Role of platelets and platelet receptors in cancer metastasis , 2018, Journal of Hematology & Oncology.

[16]  W. Jin,et al.  Tumor-Infiltrating Platelets Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma , 2018, Annals of Surgical Oncology.

[17]  M. Holinstat,et al.  Platelet Signaling and Disease: Targeted Therapy for Thrombosis and Other Related Diseases , 2018, Pharmacological Reviews.

[18]  M. Mastrogiacomo,et al.  Culture Medium Supplements Derived from Human Platelet and Plasma: Cell Commitment and Proliferation Support , 2017, Front. Bioeng. Biotechnol..

[19]  Lu Jiang,et al.  Platelet microparticle-mediated transfer of miR-939 to epithelial ovarian cancer cells promotes epithelial to mesenchymal transition , 2017, Oncotarget.

[20]  Stefan Offermanns,et al.  Intravascular Survival and Extravasation of Tumor Cells. , 2017, Cancer cell.

[21]  J. Wrana Faculty of 1000 evaluation for Metastasis: new functional implications of platelets and megakaryocytes. , 2017 .

[22]  M. Hennig,et al.  Platelets subvert T cell immunity against cancer via GARP-TGFβ axis , 2017, Science Immunology.

[23]  H. Levine,et al.  EMT and MET: necessary or permissive for metastasis? , 2017, bioRxiv.

[24]  Thomas R. Cox,et al.  Pre-metastatic niches: organ-specific homes for metastases , 2017, Nature Reviews Cancer.

[25]  R. Weinberg,et al.  Emerging Biological Principles of Metastasis , 2017, Cell.

[26]  Xuetao Cao,et al.  Characteristics and Significance of the Pre-metastatic Niche. , 2016, Cancer cell.

[27]  E. Gulbins,et al.  Melanoma cell metastasis via P-selectin-mediated activation of acid sphingomyelinase in platelets , 2016, Clinical & Experimental Metastasis.

[28]  S. Ishikawa,et al.  Platelets surrounding primary tumor cells are related to chemoresistance. , 2016, Oncology reports.

[29]  G. Scambia,et al.  Culture of human cell lines by a pathogen-inactivated human platelet lysate , 2016, Cytotechnology.

[30]  O. Peyruchaud,et al.  Metastasis: new functional implications of platelets and megakaryocytes. , 2016, Blood.

[31]  J. Segall,et al.  Tumor cell intravasation. , 2016, American journal of physiology. Cell physiology.

[32]  Andrew R. Chin,et al.  Cancer Tills the Premetastatic Field: Mechanistic Basis and Clinical Implications , 2016, Clinical Cancer Research.

[33]  Nailin Li Platelets in cancer metastasis: To help the “villain” to do evil , 2016, International journal of cancer.

[34]  K. Lauber,et al.  Platelets Guide Leukocytes to Their Sites of Extravasation , 2016, PLoS biology.

[35]  Mengjie Yan,et al.  The role of platelets in the tumor microenvironment: From solid tumors to leukemia. , 2016, Biochimica et biophysica acta.

[36]  N. Zhang,et al.  Replacing the Promoter of the Murine Gene Encoding P-selectin with the Human Promoter Confers Human-like Basal and Inducible Expression in Mice* , 2015, The Journal of Biological Chemistry.

[37]  J. Banyard,et al.  The role of EMT and MET in cancer dissemination , 2015, Connective tissue research.

[38]  A. Weyrich,et al.  Regulation of the genetic code in megakaryocytes and platelets , 2015, Journal of thrombosis and haemostasis : JTH.

[39]  K. Barbee,et al.  An in vitro model of the tumor-lymphatic microenvironment with simultaneous transendothelial and luminal flows reveals mechanisms of flow enhanced invasion. , 2015, Integrative biology : quantitative biosciences from nano to macro.

[40]  Hongwei Liang,et al.  MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3 , 2015, Molecular Cancer.

[41]  Liu Cao,et al.  P-selectin-mediated platelet adhesion promotes tumor growth , 2015, Oncotarget.

[42]  Sridhar Ramaswamy,et al.  Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis , 2014, Cell.

[43]  R. Weinberg,et al.  The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis , 2014, Nature Cell Biology.

[44]  R. Hynes,et al.  Platelets guide the formation of early metastatic niches , 2014, Proceedings of the National Academy of Sciences.

[45]  Li-jing Wang,et al.  P-Selectin-Mediated Platelet Adhesion Promotes the Metastasis of Murine Melanoma Cells , 2014, PloS one.

[46]  A. Sood,et al.  Platelets and cancer: a casual or causal relationship: revisited , 2014, Cancer and Metastasis Reviews.

[47]  B. Carr,et al.  Platelet extracts induce growth, migration and invasion in human hepatocellular carcinoma in vitro , 2014, BMC Cancer.

[48]  S. Offermanns,et al.  Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. , 2013, Cancer cell.

[49]  R. Escorpizo,et al.  Challenges and Opportunities , 1999, Deep Eutectic Solvents for Pretreatment of Lignocellulosic Biomass.

[50]  T. Brabletz EMT and MET in metastasis: where are the cancer stem cells? , 2012, Cancer cell.

[51]  A. Sood,et al.  Platelets increase the proliferation of ovarian cancer cells. , 2012, Blood.

[52]  Richard O Hynes,et al.  The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. , 2012, Cancer discovery.

[53]  B. Chong,et al.  Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells. , 2012, Cancer research.

[54]  U. Schumacher,et al.  Selectin-deficiency reduces the number of spontaneous metastases in a xenograft model of human breast cancer. , 2012, Cancer letters.

[55]  J. Freedman,et al.  Platelets and platelet-like particles mediate intercellular RNA transfer. , 2012, Blood.

[56]  G. Adam,et al.  Selectin binding is essential for peritoneal carcinomatosis in a xenograft model of human pancreatic adenocarcinoma in pfp−−/rag2−− mice , 2012, Gut.

[57]  H. Rammensee,et al.  Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. , 2012, Cancer research.

[58]  R. Black,et al.  Modelling the lymphatic system: challenges and opportunities , 2012, Journal of The Royal Society Interface.

[59]  Richard O Hynes,et al.  Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. , 2011, Cancer cell.

[60]  T. Wurdinger,et al.  Blood platelets contain tumor-derived RNA biomarkers. , 2011, Blood.

[61]  M. Chatterjee,et al.  Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli. , 2011, Blood.

[62]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[63]  Laurie J. Gay,et al.  Contribution of platelets to tumour metastasis , 2011, Nature Reviews Cancer.

[64]  F. Lupu,et al.  Differential regulation of human and murine P-selectin expression and function in vivo , 2010, The Journal of experimental medicine.

[65]  P. Sonneveld,et al.  Microparticle-associated tissue factor activity and venous thrombosis in multiple myeloma , 2010, Thrombosis and Haemostasis.

[66]  M. Schön,et al.  Deadly allies: the fatal interplay between platelets and metastasizing cancer cells. , 2010, Blood.

[67]  A. Kakkar,et al.  Antithrombotic therapy and survival in patients with malignant disease , 2010, British Journal of Cancer.

[68]  L. Borsig Antimetastatic activities of heparins and modified heparins. Experimental evidence. , 2010, Thrombosis research.

[69]  Yan-guang Gao,et al.  Modified heparins inhibit integrin αIIbβ3 mediated adhesion of melanoma cells to platelets in vitro and in vivo , 2009, International journal of cancer.

[70]  Erik Sahai,et al.  Localised and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility , 2009, Nature Cell Biology.

[71]  J. Colon,et al.  Tissue factor‐bearing microparticles derived from tumor cells: impact on coagulation activation , 2008, Journal of thrombosis and haemostasis : JTH.

[72]  George Poste,et al.  The "seed and soil" hypothesis revisited. , 2008, The Lancet. Oncology.

[73]  G. Mundy The premetastatic niche , 2008 .

[74]  J. Folkman,et al.  Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. , 2008, Blood.

[75]  A. Varki Trousseau's syndrome: multiple definitions and multiple mechanisms. , 2007, Blood.

[76]  E. Akl,et al.  Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation. , 2007, The Cochrane database of systematic reviews.

[77]  R. Sanderson,et al.  Non-Anticoagulant Heparins and Inhibition of Cancer , 2007, Pathophysiology of Haemostasis and Thrombosis.

[78]  S. Rafii,et al.  Preparing the "soil": the premetastatic niche. , 2006, Cancer research.

[79]  J. Massagué,et al.  Cancer Metastasis: Building a Framework , 2006, Cell.

[80]  J. Quigley,et al.  Matrix metalloproteinases and tumor metastasis , 2006, Cancer and Metastasis Reviews.

[81]  S. Rafii,et al.  VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche , 2005, Nature.

[82]  Birgit Kasch,et al.  Next Generation , 2005, Im OP.

[83]  K. Swoboda,et al.  Escaping the Nuclear Confines: Signal-Dependent Pre-mRNA Splicing in Anucleate Platelets , 2005, Cell.

[84]  I. Fidler,et al.  The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited , 2003, Nature Reviews Cancer.

[85]  Ajit Varki,et al.  Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[86]  Alan Wells,et al.  Growth Factor-Induced Cell Motility in Tumor Invasion , 2002, Acta oncologica.

[87]  D. Fishman,et al.  Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. , 2001, Cancer research.

[88]  David R. Nadeau,et al.  Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[89]  G. Lip,et al.  Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor , 2001, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[90]  R K Jain,et al.  Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[91]  O. McCarty,et al.  Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions. , 2000, Blood.

[92]  F. Taylor,et al.  Divergent inducible expression of P-selectin and E-selectin in mice and primates. , 1999, Blood.

[93]  N. Ferrara Role of vascular endothelial growth factor in the regulation of angiogenesis. , 1999, Kidney international.

[94]  B. Echtenacher,et al.  Lysis of tumor cells by natural killer cells in mice is impeded by platelets. , 1999, Cancer research.

[95]  P. Vermeulen,et al.  Blood platelets and serum VEGF in cancer patients , 1999, British Journal of Cancer.

[96]  A. Varki,et al.  P-selectin deficiency attenuates tumor growth and metastasis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[97]  Junliang Pan,et al.  Comparison of Promoters for the Murine and Human P-selectin Genes Suggests Species-specific and Conserved Mechanisms for Transcriptional Regulation in Endothelial Cells* , 1998, The Journal of Biological Chemistry.

[98]  Junliang Pan,et al.  Tumor Necrosis Factor-α- or Lipopolysaccharide-induced Expression of the Murine P-selectin Gene in Endothelial Cells Involves Novel κB Sites and a Variant Activating Transcription Factor/cAMP Response Element* , 1998, The Journal of Biological Chemistry.

[99]  S. Rafii,et al.  Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[100]  A. Varki,et al.  Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. , 1995, Cancer research.

[101]  Junliang Pan,et al.  Regulation of the Human P-selectin Promoter by Bcl-3 and Specific Homodimeric Members of the NF-κB/Rel Family (*) , 1995, The Journal of Biological Chemistry.

[102]  J. Pan,et al.  Characterization of the promoter for the human P-selectin gene. , 1993, The Journal of biological chemistry.

[103]  I. Fahrenfort,et al.  The bioactive phospholipid lysophosphatidic acid is released from activated platelets. , 1993, The Biochemical journal.

[104]  D. Vestweber,et al.  Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin is inducible by tumor necrosis factor alpha. , 1992, The Journal of biological chemistry.

[105]  Y. Katagiri,et al.  Characterization of platelet aggregation induced by the human melanoma cell line HMV-I: roles of heparin, plasma adhesive proteins, and tumor cell membrane proteins. , 1991, Cancer research.

[106]  O. Berthier‐Vergnes,et al.  Platelet-melanoma cell interaction is mediated by the glycoprotein IIb-IIIa complex. , 1989, Blood.

[107]  S. Karpatkin,et al.  Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. , 1988, The Journal of clinical investigation.

[108]  M. Sporn,et al.  Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells , 1986, The Journal of cell biology.

[109]  H. Al-Mondhiry Beta‐thromboglobulin and platelet‐factor 4 in patients with cancer: Correlation with the stage of disease and the effect of chemotherapy , 1983, American journal of hematology.

[110]  C. Stewart,et al.  Antimetastatic effects associated with platelet reduction. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[111]  J. Harmon,et al.  Metastasis-promoting role of extravasated platelet activation in tumor. , 2015, The Journal of surgical research.

[112]  R. Matkowski,et al.  Circulating Tumor , 2014 .

[113]  J. Freedman,et al.  New paradigms in thrombosis: novel mediators and biomarkers platelet RNA transfer , 2013, Journal of Thrombosis and Thrombolysis.

[114]  E. van Marck,et al.  Platelets and vascular endothelial growth factor (VEGF): A morphological and functional study , 2004, Angiogenesis.

[115]  Bonnie F. Sloane,et al.  Tumor cell-platelet interactions in vitro and their relationship to in vivo arrest of hematogenously circulating tumor cells , 2004, Clinical & Experimental Metastasis.

[116]  H. Beug,et al.  TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. , 1998, Current biology : CB.

[117]  S. Pulman Building the Framework , 1996 .

[118]  F. Marcucci,et al.  Treatment with modified heparins inhibits experimental metastasis formation and leads, in some animals, to long-term survival. , 1996, Invasion & metastasis.

[119]  A. Varki,et al.  Perspectives Series: Cell Adhesion in Vascular Biology Selectin Ligands: Will the Real Ones Please Stand Up? , 2022 .