THP-1; atherosclerosis; breast cancer; conditioned medium; oxLDL; oxidation; Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all); General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology
Abstract :
[en] Cardiovascular diseases are the leading causes of death worldwide, closely followed by cancer. To investigate the impact of breast cancer cell lines (SKBR3, MCF-7, and MDA-MB-231) on endothelial cell adhesion, a blended medium containing 30% breast-cancer-conditioned medium was prepared. This medium was then exposed to human umbilical vein endothelial cells (HUVECs) and monocytes (THP-1) for 48 h. Homemade oxidized low-density lipoproteins (oxLDL) were optionally added to the blended medium. Immunofluorescence was performed to assess the expression of E-selectin, connexin-43, and ICAM-1 on HUVECs, as well as LOX-1, CD36, and CD162 on THP-1. Additionally, unoxidized LDL was exposed to the three breast cancer cell lines for 48 h, and the formation of oxLDL was quantified. Our results revealed an upregulation of all six adhesion markers involved in the initiation of atherosclerosis when HUVECs and THP-1 were exposed to the breast-cancer-conditioned medium. Furthermore, this expression was further increased by exposure to oxLDL. We also observed a significant elevation in oxLDL levels when LDL was exposed to breast cancer cells. In conclusion, our findings successfully demonstrate an increased LDL oxidation in the presence of breast cancer cells, accompanied by an augmented expression of receptors involved in atherosclerosis initiation. These findings shed new light on the clinically observed interplay between atherosclerosis and cancer.
Doumani, Lesly; Department of Cardiology, Research Institute for Health Sciences and Technology, University of Mons (UMONS), 7000 Mons, Belgium
Kindt, Nadège; Department of Cardiology, Research Institute for Health Sciences and Technology, University of Mons (UMONS), 7000 Mons, Belgium ; Department of Clinical and Experimental Oncology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium
Journe, Fabrice ; Université de Mons - UMONS ; Department of Clinical and Experimental Oncology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium
Cardiovascular Diseases Available online: https://www.who.int/health-topics/cardiovascular-diseases (accessed on 9 November 2022)
Cancer Available online: http://www.who.int/news-room/fact-sheets/detail/cancer (accessed on 18 May 2022)
Dafni U. Tsourti Z. Alatsathianos I. Breast Cancer Statistics in the European Union: Incidence and Survival across European Countries Breast Care 2019 14 344 353 10.1159/000503219 31933579
Ferlay J. Colombet M. Soerjomataram I. Dyba T. Randi G. Bettio M. Gavin A. Visser O. Bray F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018 Eur. J. Cancer 2018 103 356 387 10.1016/j.ejca.2018.07.005 30100160
Carioli G. Malvezzi M. Rodriguez T. Bertuccio P. Negri E. La Vecchia C. Trends and predictions to 2020 in breast cancer mortality in Europe Breast 2017 36 89 95 10.1016/j.breast.2017.06.003 28988610
Roubín S.R. Cordero A. The Two-way Relationship Between Cancer and Atherosclerosis Rev. Española Cardiol. (Engl. Ed.) 2019 72 487 494 10.1016/j.rec.2018.12.010
Florido R. Daya N.R. Ndumele C.E. Koton S. Russell S.D. Prizment A. Blumenthal R.S. Matsushita K. Mok Y. Felix A.S. et al. Cardiovascular Disease Risk Among Cancer Survivors J. Am. Coll. Cardiol. 2022 80 22 32 10.1016/j.jacc.2022.04.042
Kattoor A.J. Pothineni N.V.K. Palagiri D. Mehta J.L. Oxidative Stress in Atherosclerosis Curr. Atheroscler. Rep. 2017 19 42 10.1007/s11883-017-0678-6
Rafieian-Kopaei M. Setorki M. Doudi M. Baradaran A. Nasri H. Atherosclerosis: Process, Indicators, Risk Factors and New Hopes Int. J. Prev. Med. 2014 5 927 946
Tapia-Vieyra J.V. Delgado-Coello B. Mas-Oliva J. Atherosclerosis and Cancer; A Resemblance with Far-reaching Implications Arch. Med Res. 2017 48 12 26 10.1016/j.arcmed.2017.03.005
Murdocca M. De Masi C. Pucci S. Mango R. Novelli G. Di Natale C. Sangiuolo F. LOX-1 and cancer: An indissoluble liaison Cancer Gene Ther. 2021 28 1088 1098 10.1038/s41417-020-00279-0
Galkina E. Ley K. Vascular Adhesion Molecules in Atherosclerosis Arterioscler. Thromb. Vasc. Biol. 2007 27 2292 2301 10.1161/ATVBAHA.107.149179
Woollard K.J. Geissmann F. Monocytes in atherosclerosis: Subsets and functions Nat. Rev. Cardiol. 2010 7 77 86 10.1038/nrcardio.2009.228 20065951
Katayama Y. Hidalgo A. Furie B.C. Vestweber D. Furie B. Frenette P.S. PSGL-1 participates in E-selectin–mediated progenitor homing to bone marrow: Evidence for cooperation between E-selectin ligands and α4 integrin Blood 2003 102 2060 2067 10.1182/blood-2003-04-1212 12763924
Faxon D.P. Fuster V. Libby P. Beckman J.A. Hiatt W.R. Thompson R.W. Topper J.N. Annex B.H. Rundback J.H. Fabunmi R.P. et al. Atherosclerotic Vascular Disease Conference Circulation 2004 109 2617 2625 10.1161/01.CIR.0000128520.37674.EF 15173044
Kzhyshkowska J. Neyen C. Gordon S. Role of macrophage scavenger receptors in atherosclerosis Immunobiology 2012 217 492 502 10.1016/j.imbio.2012.02.015 22437077
Wingo P.A. Ries L.A.G. Rosenberg H.M. Miller D.S. Edwards B.K. Cancer incidence and mortality, 1973–1995 Cancer 1998 82 1197 1207 10.1002/(SICI)1097-0142(19980315)82:6<1197::AID-CNCR26>3.0.CO;2-0
Rotheneder M. Kostner G.M. Effects of low- and high-density lipoproteins on the proliferation of human breast cancer cellsIn vitro: Differences between hormone-dependent and hormone-independent cell lines Int. J. Cancer 1989 43 875 879 10.1002/ijc.2910430523
Dos Santos C.R. Fonseca I. Dias S. De Almeida J.C.M. Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression BMC Cancer 2014 14 132 10.1186/1471-2407-14-132
Khaidakov M. Mehta J.L. Oxidized LDL Triggers Pro-Oncogenic Signaling in Human Breast Mammary Epithelial Cells Partly via Stimulation of MiR-21 PLoS ONE 2012 7 e46973 10.1371/journal.pone.0046973
Pucci S. Polidoro C. Greggi C. Amati F. Morini E. Murdocca M. Biancolella M. Orlandi A. Sangiuolo F. Novelli G. Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes Cell Death Dis. 2019 10 53 10.1038/s41419-018-1279-1
Klooster C.C.V. Ridker P.M. Hjortnaes J. van der Graaf Y. Asselbergs F.W. Westerink J. Aerts J.G.J.V. Visseren F.L.J. The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: A cohort study Eur. Heart J. 2019 40 3901 3909 10.1093/eurheartj/ehz587
Raza U. Asif M.R. Bin Rehman A. Sheikh A. Hyperlipidemia and hyper glycaemia in Breast Cancer Patients is related to disease stage Pak. J. Med. Sci. 2018 34 209 214 10.12669/pjms.341.14841 29643909
Pope A. Thomson L. Cantu S. Setia G. Torosyan N. Merz N.B. Atkins K. Anderson E.M. Cheng S. Tamarappoo B. Detection of subclinical atherosclerosis from PET-CT in patients with breast cancer J. Cardiovasc. Comput. Tomogr. 2022 16 189 190 10.1016/j.jcct.2021.09.009 34688578
Cauley J.A. Zmuda J.M. Lui L.-Y. Hillier T.A. Ness R.B. Stone K.L. Cummings S.R. Bauer D.C. Lipid-lowering drug use and breast cancer in older women: A prospective study J. Women’s Health 2003 12 749 756 10.1089/154099903322447710
Bonovas S. Filioussi K. Tsavaris N. Sitaras N.M. Use of statins and breast cancer: A meta-analysis of seven randomized clinical trials and nine observational studies J. Clin. Oncol. 2005 23 8606 8612 10.1200/JCO.2005.02.7045 16260694
Scalia A. Kindt N. Trelcat A. Nachtergael A. Duez P. Journé F. Carlier S. Development of a Method for Producing oxLDL: Characterization of Their Effects on HPV-Positive Head and Neck Cancer Cells Int. J. Mol. Sci. 2022 23 12552 10.3390/ijms232012552
Holliday D.L. Speirs V. Choosing the right cell line for breast cancer research Breast Cancer Res. 2011 13 215 10.1186/bcr2889
Genin M. Clement F. Fattaccioli A. Raes M. Michiels C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide BMC Cancer 2015 15 577 10.1186/s12885-015-1546-9
Rathod K.S. Siddiqui U. Hartley A. Khambata R. Ahluwalia A. Investigation of the influence of sex on cantharidin-induced inflammation in healthy volunteers FASEB J. 2016 30 716.9 10.1096/fasebj.30.1_supplement.716.9
Li D. Mehta J.L. Intracellular signaling of LOX-1 in endothelial cell apoptosis Circ. Res. 2009 104 566 568 10.1161/CIRCRESAHA.109.194209
Schaeffer D.F. Riazy M. Parhar K.S. Chen J.H. Duronio V. Sawamura T. Steinbrecher U.P. LOX-1 augments oxLDL uptake by lysoPC-stimulated murine macrophages but is not required for oxLDL clearance from plasma J. Lipid Res. 2009 50 1676 1684 10.1194/jlr.M900167-JLR200
Yao Y. Xu X.-H. Jin L. Macrophage Polarization in Physiological and Pathological Pregnancy Front. Immunol. 2019 10 792 10.3389/fimmu.2019.00792 31037072
Stöger J.L. Gijbels M.J. van der Velden S. Manca M. van der Loos C.M. Biessen E.A. Daemen M.J. Lutgens E. de Winther M.P. Distribution of macrophage polarization markers in human atherosclerosis Atherosclerosis 2012 225 461 468 10.1016/j.atherosclerosis.2012.09.013 23078881
Bisgaard L.S. Mogensen C.K. Rosendahl A. Cucak H. Nielsen L.B. Rasmussen S.E. Pedersen T.X. Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression—Implications for atherosclerosis research Sci. Rep. 2016 6 35234 10.1038/srep35234 27734926
Gleissner C.A. Shaked I. Little K.M. Ley K. CXC Chemokine Ligand 4 Induces a Unique Transcriptome in Monocyte-Derived Macrophages J. Immunol. 2010 184 4810 4818 10.4049/jimmunol.0901368 20335529
Weagel E. Smith C. Liu P.G. Robison R. O’neill K. Macrophage Polarization and Its Role in Cancer J. Clin. Cell. Immunol. 2015 6 338 10.4172/2155-9899.1000338
Guiducci C. Vicari A.P. Sangaletti S. Trinchieri G. Colombo M.P. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection Cancer Res. 2005 65 3437 3446 10.1158/0008-5472.CAN-04-4262
Pe K.C.S. Saetung R. Yodsurang V. Chaotham C. Suppipat K. Chanvorachote P. Tawinwung S. Triple-negative breast cancer influences a mixed M1/M2 macrophage phenotype associated with tumor aggressiveness PLoS ONE 2022 17 e0273044 10.1371/journal.pone.0273044
Nguyen L.T.H. Muktabar A. Tang J. Wong Y.S. Thaxton C.S. Venkatraman S.S. Ng K.W. The Potential of Fluocinolone Acetonide to Mitigate Inflammation and Lipid Accumulation in 2D and 3D Foam Cell Cultures BioMed Res. Int. 2018 2018 3739251 10.1155/2018/3739251
Chen J. Zhang X. Millican R. Lynd T. Gangasani M. Malhotra S. Sherwood J. Hwang P.T. Cho Y. Brott B.C. et al. Recent Progress in in vitro Models for Atherosclerosis Studies Front. Cardiovasc. Med. 2022 8 790529 10.3389/fcvm.2021.790529
Chen C.-N. Chang S.-F. Lee P.-L. Chang K. Chen L.-J. Usami S. Chien S. Chiu J.-J. Neutrophils, lymphocytes, and monocytes exhibit diverse behaviors in transendothelial and subendothelial migrations under coculture with smooth muscle cells in disturbed flow Blood 2006 107 1933 1942 10.1182/blood-2005-08-3137
Ragaseema V.M. Columbus S. Ramesh R. Krishnan L. Potential of Tissue Engineered Blood Vessel as Model to Study Effect of Flow and Wall Thickness on Cellular Communication Curr. Tissue Eng. 2013 3 39 46 10.2174/2211542002666131209233849
Robert J. Weber B. Frese L. Emmert M.Y. Schmidt D. von Eckardstein A. Rohrer L. Hoerstrup S.P. A Three-Dimensional Engineered Artery Model for In Vitro Atherosclerosis Research PLoS ONE 2013 8 e79821 10.1371/journal.pone.0079821 24244566
Zheng F. Fu F. Cheng Y. Wang C. Zhao Y. Gu Z. Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems Small 2016 12 2253 2282 10.1002/smll.201503208
Cochrane A. Albers H.J. Passier R. Mummery C.L. van den Berg A. Orlova V.V. van der Meer A.D. Advanced in vitro models of vascular biology: Human induced pluripotent stem cells and organ-on-chip technology Adv. Drug Deliv. Rev. 2019 140 68 77 10.1016/j.addr.2018.06.007 29944904
Poussin C. Kramer B. Lanz H.L. Heuvel A.V.D. Laurent A. Olivier T. Vermeer M. Peric D. Baumer K. Dulize R. et al. 3D human microvessel-on-a-chip model for studying monocyte-to-endothelium adhesion under flow—Application in systems toxicology ALTEX-Altern. Anim. Exp. 2020 37 47 63 10.14573/altex.1811301 31445503
Heo K.-S. Fujiwara K. Abe J.-I. Shear stress and atherosclerosis Mol. Cells 2014 37 435 440 10.14348/molcells.2014.0078