Journal of Fluorescence

, Volume 24, Issue 5, pp 1473–1479 | Cite as

Detection of Binding of a Synthetic Granzyme B-like Peptide Fluorescent Conjugate within Platelet-like Structures in Cancer-related Peripheral Blood Specimens and Tissue Sections

  • Wai Chun Jennifer Lo
  • Donald Gene Luther


Platelets and cytotoxic T lymphocytes (CTL) are important whole blood components in peripheral blood. Studies have shown that platelets, from precursor megakaryocytes, are significant factors in cancer prognosis, cancer progression, and metastasis; but a direct platelet-cancer relationship remains unclear. CTL play an essential role in cancer surveillance by inducing cancer cell death with granzyme B. A recent report has shown the presence of binding targets with binding affinity to a synthetic granzyme B-like peptide fluorescent conjugate (GP1R) in different types of cancer cells grown in vitro. It suggests that these binding targets may serve as a “universal-pathologic-biomarker”. It is not known if similar biomarkers may be present in platelets of cancer patients. We show with fluoroscopic images that GP1R can bind to binding targets: 1) within platelets in methanol-fixed whole blood smears of patients with breast cancer and lung cancer, and 2) within platelet-like structures in formalin-fixed-paraffin-embedded (FFPE) nude mouse xenogeneic breast tumor tissues. Samples without cancer-association displayed no discernible GP1R-binding in platelet-like structures. Our data demonstrate for the first time that a similar “universal-pathologic-biomarker” detectable by GP1R-binding is present in circulating platelets of cancer patients. The data depict a co-existence of animal-platelets and human-breast cancer cells, both have a common pathologic biomarker detectable by GP1R, in the tumor growth. The fluoroscopic images indicate a visual direct connection between pathologic platelets and cancer. These preliminary results may lead to developments of novel platelet-based cancer diagnostics and therapeutics and a better understanding of the potential multifunction of GP1R and its relationship to megakaryocytes and PD1.


Biomarker Cancer Fluorescence microscopy Granzymes Peptide Platelets 


  1. 1.
    Matowicka-Karna J et al (2013) Platelets and inflammatory markers in patients with gastric cancer. Clin Dev Immunol vol. 2013, Article ID 401623, 6 pages. doi: 10.1155/2013/401623
  2. 2.
    Nieswandt B, Hafner M, Echtenacher B, Mannel DN (1999) Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res 59:1295–1300PubMedGoogle Scholar
  3. 3.
    Palumbo JS et al (2005) Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105:178–185PubMedCrossRefGoogle Scholar
  4. 4.
    Voutsadakis IA (2014) Thrombocytosis as a prognostic marker in gastrointestinal cancers. World J Gastrointest Oncol 6:34–40PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Taucher S et al (2003) Impact of pretreatment thrombocytosis on survival in primary breast cancer. Thromb Haemost 89:1098–1106PubMedGoogle Scholar
  6. 6.
    Stravodimou A, Voutsadakis IA (2013) Pretreatment thrombocytosis as a prognostic factor in metastatic breast cancer. Int J Breast Cancer vol. 2013, Article ID 289563, 6 pages. doi: 10.1155/2013/289563
  7. 7.
    Maráz A et al (2013) Thrombocytosis has a negative prognostic value in lung cancer. Anticancer Res 33:1725–1729PubMedGoogle Scholar
  8. 8.
    Todenhöfer T et al (2012) A new prognostic model for cancer-specific survival after radical cystectomy including pretreatment thrombocytosis and standard pathological risk factors. BJU Int 110:E533–E540PubMedCrossRefGoogle Scholar
  9. 9.
    Wang L et al (2005) Mechanism of cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. Zhonghua Yi Xue Za Zhi 85:3048–3051PubMedGoogle Scholar
  10. 10.
    Lo WCJ, Luther DG (2014) Detection of cancer cell death mediated by a synthetic granzyme B-like peptide fluorescent conjugate and the same binding in bacteria. J Fluoresc 24:465–471CrossRefGoogle Scholar
  11. 11.
    Oft M, Heider KH, Beug H (1998) TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr Biol 8:1243–1252PubMedCrossRefGoogle Scholar
  12. 12.
    Kang Y et al (2005) Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc Natl Acad Sci U S A 102:13909–13914PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Assoian RK et al (1983) Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem 58:7155–7160Google Scholar
  14. 14.
    Iwai Y et al (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockage. Proc Natl Acad Sci U S A 99:12293–12297PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Topalian SL et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Hamid O et al (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369:134–144PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.BioJENC, Louisiana Emerging Technology CenterBaton RougeUSA
  2. 2.University ProductsBaton RougeUSA

Personalised recommendations