PDGF-AB rich-trombocyte lysate supplementation from breast cancer patients increased the proliferation of breast cancer stem cells
AbstractBackground: Thrombocytosis in breast cancer (BC) patient was thought to play a role in the invasiveness of breast cancer stem cells (BCSCs). Modification of tumor microenvironment was proposed to increase the efficacy of anticancer therapy. This study was aimed to analyze the effect of platelet lysate (PL) as well as its PDGF-AB content as a tumor microenvironment on (CD24-/CD44+) BCSC proliferation.
Methods: This was an experimental study that treated culture of BCSCs with PL from breast cancer (BC) patients or healthy donors. Venous blood from all subjects were subjected to prior hematology test and then processed to obtain platelet rich plasma (PRP). Platelet counts in PRP were determined. PRP was processed to obtain PL. PDGF-AB contents in PL were measured. PL at concentrations of 0.01% (v/v) was supplemented into DMEM-F12 medium and used for culturing BCSCs (CD24-/CD44+ cells). After 48 hours, total cell count, population doubling time (PDT), and cell viability were calculated and their correlation with platelet count and PDGF-AB levels were analyzed.
Results: BC patients (n=5) had higher platelet counts and PDGF-AB levels in PL compared to healthy donors (n=15), (p=0.02). PL from BC patients could stimulate the proliferation of BCSCs higher than healthy donors (p<0.001) and showed lower PDT value (p=0.001). Cell proliferation and PDT showed strong correlation with PDGF-AB level. This observation suggests that PDGF-AB has a role on BCSCs proliferation. PL showed no effect on BCSCs viability.
Conclusion: Breast cancer patient platelet lysate stimulated BCSC proliferation.
GLOBOCAN [Internet]. Estimated cander incidence, mortality and prevalence worldwide in 2012 [cited 2016 March 1]. Available from: http://globocan.iarc.fr/Default.aspx.
Klevebring F, Rosin G, Ma R, Lindberg J, Czene K, Kere J, et al. Sequencing of breast cancer stem cell populations indicates a dynamic conversion between differentiation states in vivo. Breast Cancer Res. 2014;15(R72). https://doi.org/10.1186/bcr3687
Tesfamariam B. Involvement of platelets in tumor cell metastasis. Pharmacol Ther. 2016; 157:112–9. https://doi.org/10.1016/j.pharmthera.2015.11.005
Van Pham P, Bui KH, Ngo DQ, Vu NB, Truong NH, Phan NL, et al. Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage. Stem Cell Res Ther. 2013;4(4):91. https://doi.org/10.1186/scrt277
Jin R, Zhang L, Zhang Y-G. Does platelet-rich plasma enhance the survival of grafted fat? An update review. Int J Clin Exp Med. 2013;6(4):252–8.
Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma from basic science to clinical applications. Am J Sports Med. 2009;37(11):2259–72. https://doi.org/10.1177/0363546509349921
Kanojia D, Chen H. The Microenvironment of Breast Cancer Stem Cells. In: Gunduz M, Gunduz E, editors. Breast cancer - focusing tumor microenvironment, stem cells and metastasis. Rijeka: InTech; 2011. p. 237–46. https://doi.org/10.5772/20574
Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and tumor microenvironment. J Clin Invest. 2011;121(10):3804–9. https://doi.org/10.1172/JCI57099
De Donatis A, Comito G, Burricchi F, Vinci M, Parenti A, Caselli A, et al. Proliferation Versus Migration in Platelet-Derived Growth Factor Signaling. J Biol Chem. 2008;283(29):19948–56. https://doi.org/10.1074/jbc.M709428200
Swartz M, Iida N, Roberts E, Sangaletti S, Wong M, Yull F. Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res. 2012;27:2473–80. https://doi.org/10.1158/0008-5472.CAN-12-0122
Sari P, Luviah E, Nugraha Y, Pawitan JA, Lilianty J, Purwoko RY. Various growth factor yields in various platelet rich plasma processing methods. BTAIJ. 2014;9(11): 475-8.
Chao YL, Shepard C, Wells A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer. 2010;9:179. https://doi.org/10.1186/1476-4598-9-179
Colciago A, Celotti F, Casati L, Giancola R, Castano S, Antonini G, et al. In vitro effects of PDGF Isoforms (AA, BB, AB and CC) on migration and proliferation of SaOS-2 osteoblasts and on migration of human osteoblasts. Int J Biomed Sci. 2009;5(4):380–9.
Sierko E, Wojtukiewicz M. Platelets and angiogenesis in malignancy. Semim Thromb Hemost. 2004;30:95–108. https://doi.org/10.1055/s-2004-822974
McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, et al. Roles of the Raf/MEK/Erk pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007;1773(8):1263–84. https://doi.org/10.1016/j.bbamcr.2006.10.001
Heldin C-H. Targeting the PDGF signaling pathway in tumor treatment. Cell Comm Signal. 2013;11:97. https://doi.org/10.1186/1478-811X-11-97
Carvalho I, Milanezi F, Martins A, Reis RM, Schmitt F. Overexpression of platelet-derived growth factor receptor α in breast cancer is associated with tumour progression. Breast Cancer Res. 2005;7(5):R788–95. https://doi.org/10.1186/bcr1304
Cross TG, Scheel-Toelner D, Henriquez N, Deacon E, Salmon M, Lord J. Serine/threonine protein kinases andapoptosis. Exp Cell Res. 2000;256:34–41. https://doi.org/10.1006/excr.2000.4836
Pearson G, Robinson F, Beers Gibson T, Xu B. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153–83. https://doi.org/10.1210/er.22.2.153
Suryani D, Pawitan JA, Lilianty J, Purwoko RY, Liem IK, Damayanti L. Comparison of fetal bovine serum and platelet-rich plasma on human lipoaspirate-derived mesenchymal stem cell proliferation. Med J Indones. 2013;22;146–51. https://doi.org/10.13181/mji.v22i3.583
Bertrand-Duchesne M-P, Grenier D, Gagnon G. Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitro. J Periodontal Res. 2010;45(1):87–93. https://doi.org/10.1111/j.1600-0765.2009.01205.x
Copyright (c) 2018 Wiwi A. Kartolo, Jeanne A. Pawitan, Alida R. Harahap, Septelia I. Wanandi
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.