Giant foam-like macrophages in advanced ovarian cancer

Giant foam-like macrophages in advanced ovarian cancer

Автор: Rakina M.A., Kazakova E.O., Sudarskikh T.S., Bezgodova N.V., Villert A.B., Kolomiets L.A., Larionova I.V.

Журнал: Сибирский онкологический журнал @siboncoj

Рубрика: Лабораторные и экспериментальные исследования

Статья в выпуске: 2 т.21, 2022 года.

Бесплатный доступ

Introduction. Ovarian cancer (OC) is the third most common gynecological cancer with the worst prognosis and highest mortality rate. The progression of OC can be accompanied by the detrimental functions of the components of the tumor microenvironment, including tumor-associated macrophages (TAMs). The purpose of the study to analyze distribution and morphological phenotype of TAMs in tumor tissue of patients with high-grade serous ovarian cancer (HGSOC). Material and Methods. Formalin fixed paraffin embedded tissue sections were obtained from ovarian cancer patients after tumor resection. The protein expression of general macrophage marker CD68 and M2-like markers CD206, CD163 and stabilin-1, belonging to scavenger receptors, was analysed by immunohistochemical staining in tumor tissue. Histological assessment of TAM distribution was performed by pathologist. Immunofluorescent analysis/confocal microscopy was applied to establish the co-expression of CD68 with the main macrophage scavenger receptors. Results. We were able to find giant CD68-positive macrophages with foamy cytoplasm in ovarian tumor tissue. The accumulation of these TAMs was specific only for patients with advanced stage (IIIC and IV stages). The presence of foam-like TAMs had a statistical tendency to be associated with ovarian cancer progression, including metastasis and recurrence. The distribution of stabilin-1-positive macrophages was matched to CD68 expression in almost all cases, as was shown by IHC. Confocal microscopy confirmed that stabilin-1 was expressed in at least 50 % of giant TAMs. IF analysis of tumor samples also demonstrated co-expression of other scavenger receptors, CD163 and CD36, in foam-like cells. Similar to IHC, in most samples the expression of CD206 in TAMs of foam-like morphology was limited. Conclusion. For the first time we demonstrated the accumulation of giant macrophages with fluffy foam cytoplasm in the tumor tissue of treated patients with advanced ovarian cancer. Such macrophages express diverse scavenger receptors (stabilin-1, CD163, CD36), thus indicating a high clearance activity of giant TAMs.

Еще

Ovarian neoplasms, tumor-associated macrophages, foam-like cells, receptors, scavenger

Короткий адрес: https://sciup.org/140293898

IDR: 140293898

Список литературы Giant foam-like macrophages in advanced ovarian cancer

  • Momenimovahed Z., TiznobaikA., Taheri S., Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health. 2019; 11: 287-99. doi: 10.2147/IJWH.S197604.
  • Виллерт А.Б., Коломиец Л.А., Юнусова Н.В., Иванова А.А. Асцит как предмет исследований при раке яичников. Сибирский онкологический журнал. 2019; 18(1): 116-23. [Villert A.B., KolomietsL.A., Yunusova N.V., Ivanova A.A. Ascites as a subject of studies in ovarian cancer. Siberian Journal of Oncology. 2019; 18(1): 116-23. (in Russian)]. doi: 10.21294/1814-4861-2019-18-1-116-123.
  • SungH., Ferlay J., SiegelR.L., LaversanneM., Soerjomataram I., JemalA., BrayF. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209-49. doi: 10.3322/caac.21660.
  • Спиридонова Н.В., Демура А.А., Щукин В.Ю. Оценка сопутствующей гинекологической патологии в группе пациенток репродуктивного возраста с опухолями и опухолевидными образованиями яичников. Медицинский алфавит. 2020; 16: 10-4. [Spiridonova N.V., Demura A.A., Schukin V.Yu. Evaluation of concomitant gynecological pathology in group of patients of reproductive age with tumors and tumor formations. Medical Alphabet. 2020; 16: 10-4. (in Russian)]. doi: 10.33667/2078-5631-2020-16-10-14.
  • ВяткинаН.В., ФроловаИ.Г., Коломиец ЛА., Молчанов С.В., Виллерт А.Б. Возможности комплексного ультразвукового исследования в дооперационном стадировании диссеминированного рака яичников. Сибирский онкологический журнал. 2016; 15(4): 26-32. [Vyatkina N.V., Frolova I.G., Kolomiets L.A., Molchanov S.V., Villert A.B. Diagnostic value of ultrasound examination in preoperative staging of disseminated ovarian cancer. Siberian Journal of Oncology. 2016; 15(4): 26-32. (in Russian)]. doi: 10.21294/1814-4861-2016-15-4-26-32.
  • YinM., Shen J., Yu S., Fei J., Zhu X., Zhao J., Zhai L., Sadhukhan A., Zhou J. Tumor-Associated Macrophages (TAMs): A Critical Activator In Ovarian Cancer Metastasis. Onco Targets Ther. 2019; 12: 8687-99. doi: 10.2147/OTT.S216355.
  • Cortez A.J., Tudrej P., Kujawa K.A., Lisowska K.M. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol. 2018; 81(1): 17-38. doi: 10.1007/s00280-017-3501-8.
  • Ефимова О.А., СафоноваМ.А. Эпидемиология рака яичников на ранних стадиях. Acta Medica Eurasica. 2018; 4: 9-18. [Efimova O.A., Safonova M.A. Epidemiology of ovarian cancer in early stages. Acta Medica Eurasica. 2018; 4: 9-18. (in Russian)].
  • BrandA.H., DiSilvestro P.A., Sehouli J., Berek J.S. Cytoreductive surgery for ovarian cancer: quality assessment. Ann Oncol. 2017; 28(8): 25-9. doi: 10.1093/annonc/mdx448.
  • Henderson J.T., Webber E.M., Sawaya G.F. Screening for Ovarian Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018; 319(6): 595-606. doi: 10.1001/jama.2017.21421.
  • Larionova I., Tuguzbaeva G., Ponomaryova A., Stakheyeva M., CherdyntsevaN., Pavlov V., ChoinzonovE., Kzhyshkowska J. Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers. Front Oncol. 2020; 10. doi: 10.3389/fonc.2020.566511.
  • Zhang M, He Y., Sun X., Li Q, Wang W, Zhao A., Di W. A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res. 2014; 7: 19. doi: 10.1186/1757-2215-7-19.
  • Yuan X., Zhang J., Li D, Mao Y, Mo F., Du W., Ma X. Prognostic significance of tumor-associated macrophages in ovarian cancer: A meta-analysis. Gynecol Oncol. 2017; 147(1): 181-7. doi: 10.1016/j. ygyno.2017.07.007.
  • AllavenaP., Mantovani A. Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment. Clin Exp Immunol. 2012; 167(2): 195-205. doi: 10.1111/j.1365-2249.2011.04515.x.
  • CassettaL., FragkogianniS., SimsA.H., SwierczakA., ForresterLM., Zhang H., Soong D.Y.H., Cotechini T., Anur P., Lin E.Y., FidanzaA., Lo-pez-YrigoyenM., MillarM.R., UrmanA., Ai Z., SpellmanP.T., HwangE.S., Dixon J.M., Wiechmann L., Coussens L.M., Smith H.O., Pollard J.W. Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets. Cancer Cell. 2019; 35(4): 588-602. doi: 10.1016/j. ccell.2019.02.009.
  • Malfitano A.M., Pisanti S., Napolitano F., Di Somma S., Marti-nelli R., Portella G. Tumor-Associated Macrophage Status in Cancer Treatment. Cancers (Basel). 2020; 12(7): 1987. doi: 10.3390/can-cers12071987.
  • EisingerS., SarhanD., Boura VF., Ibarlucea-BenitezI., TyystjärviS., Oliynyk G., Arsenian-HenrikssonM., Lane D., Wikström S.L., KiesslingR., Virgilio T., Gonzalez S.F., Kaczynska D., Kanatani S., Daskalaki E., Wheelock C.E., Sedimbi S., ChambersB.J., Ravetch J.V., KarlssonM.C.I. Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells. Proc Natl Acad Sci USA. 2020; 117(50): 32005-16. doi: 10.1073/pnas.2015343117.
  • Guerrini V., GennaroM.L. Foam Cells: One Size Doesn't Fit All. Trends Immunol. 2019; 40(12): 1163-79. doi: 10.1016/j.it.2019.10.002.
  • Lee-RueckertM., Lappalainen J., Kovanen P.T., Escola-Gil J.C. Lipid-Laden Macrophages and Inflammation in Atherosclerosis and Cancer: An Integrative View. Front Cardiovasc Med. 2022; 9. doi: 10.3389/ fcvm.2022.777822.
  • DonadonM., Torzilli G., Cortese N., Soldani C., Di Tommaso L., Franceschini B., Carriero R., Barbagallo M., Rigamonti A., Anselmo A., Colombo F.S., Maggi G., Lleo A., Cibella J., Peano C., Kunderfranco P., Roncalli M., Mantovani A., Marchesi F. Macrophage morphology correlates with single-cell diversity and prognosis in colorectal liver metastasis. J Exp Med. 2020; 217(11). doi: 10.1084/jem.20191847.
  • KrawczykK.M., NilssonH., AllaouiR., LindgrenD., ArvidssonM., Leandersson K., Johansson M.E. Papillary renal cell carcinoma-derived chemerin, IL-8, and CXCL16 promote monocyte recruitment and differentiation into foam-cell macrophages. Lab Invest. 2017; 97(11): 1296-305. doi: 10.1038/labinvest.2017.78.
  • OuimetM., Koster S., SakowskiE., RamkhelawonB., van Solingen C., Oldebeken S., Karunakaran D., Portal-Celhay C., Sheedy F.J., Ray T.D., Cecchini K., Zamore P.D., Rayner K.J., Marcel Y.L., Philips J.A., Moore K.J. Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat Immunol. 2016; 17(6): 677-86. doi: 10.1038/ni.3434.
  • Nolan S.J., Romano J.D., Coppens I. Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii. PLoS Pathog. 2017; 13(6). doi: 10.1371/journal.ppat.1006362.
  • Politz O, GratchevA., McCourtP.A., SchledzewskiK., GuillotP., Johansson S., Svineng G., Franke P., Kannicht C., Kzhyshkowska J., Longati P., Velten F. W., Johansson S., Goerdt S. Stabilin-1 and -2 constitute a novel family of fasciclin-like hyaluronan receptor homologues. Biochem J. 2002; 362(1): 155-64. doi: 10.1042/0264-6021:3620155.
  • Taban Q., Mumtaz P.T., Masoodi K.Z., Haq E., Ahmad S.M. Scavenger receptors in host defense: from functional aspects to mode of action. Cell Commun Signal. 2022; 20(1): 2. doi: 10.1186/s12964-021-00812-0.
  • Madsen D.H., Jürgensen H.J., Siersbœk M.S., Kuczek D.E., Grey CloudL., Liu S., Behrendt N., Gr0ntvedL., Weigert R., Bugge T.H. Tumor-Associated Macrophages Derived from Circulating Inflammatory Monocytes Degrade Collagen through Cellular Uptake. Cell Rep. 2017; 21(13): 3662-71. doi: 10.1016/j.celrep.2017.12.011.
  • CornK.C., WindhamM.A., RafatM. Lipids in the tumor microenvironment: From cancer progression to treatment. Prog Lipid Res. 2020; 80. doi: 10.1016/j.plipres.2020.101055.
  • Wu H., Han Y., Rodriguez Sillke Y., Deng H., Siddiqui S., Treese C., Schmidt F., Friedrich M., Keye J., Wan J., Qin Y., Kühl A.A., Qin Z., Siegmund B., Glauben R. Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages. EMBO Mol Med. 2019; 11(11). doi: 10.15252/emmm.201910698.
  • Shimizu R., Tanaka K., Oikawa Y., Tomioka H., Kayamori K., Ikeda T., Yoshioka T., Ebihara A., Harada H. Epithelioid cell granuloma with caseating necrosis possibly caused by periapical periodontitis: a case report. J Med Case Rep. 2018; 12(1): 365. doi: 10.1186/s13256-018-1891-9.
  • Gordon S. Phagocytosis: An Immunobiologic Process. Immunity. 2016; 44(3): 463-75. doi: 10.1016/j.immuni.2016.02.026.
  • Huff M.W., Daugherty A., Lu H. Chapter 18 - Atherosclerosis. Biochemistry of Lipids, Lipoproteins and Membranes (Sixth Edition). Elsevier. 2016. P. 519-48. doi: 10.1016/B978-0-444-63438-2.00018-3.
  • Zhang L., Han L., He J., Lv J., Pan R., Lv T. A high serum-free fatty acid level is associated with cancer. J Cancer Res Clin Oncol. 2020; 146(3): 705-10. doi: 10.1007/s00432-019-03095-8.
  • Su P., Wang Q, Bi E, Ma X., Liu L, Yang M, Qian J., Yi Q. Enhanced Lipid Accumulation and Metabolism Are Required for the Differentiation and Activation of Tumor-Associated Macrophages. Cancer Res. 2020; 80(7): 1438-50. doi: 10.1158/0008-5472.CAN-19-2994.
  • Liu-Jarin X., Stoopler M.B., Raftopoulos H., Ginsburg M., Go-renstein L., Borczuk A.C. Histologic assessment of non-small cell lung carcinoma after neoadjuvant therapy. Mod Pathol. 2003; 16(11): 1102-8. doi: 10.1097/01.MP.0000096041.13859.AB.
  • Lo Russo G., Moro M., Sommariva M., Cancila V., Boeri M., Centonze G., Ferro S., GanzinelliM., Gasparini P., Huber V., MilioneM., Porcu L., Proto C., Pruneri G., Signorelli D., Sangaletti S., Sfondrini L., Storti C., Tassi E., Bardelli A., Marsoni S., Torri V., Tripodo C., Colombo M.P., Anichini A., Rivoltini L., Balsari A., Sozzi G., Garassino M.C. Antibody-Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non-small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade. Clin Cancer Res. 2019; 25(3): 989-99. doi: 10.1158/1078-0432.CCR-18-1390.
  • Feinberg H., Jegouzo S.A.F., Lasanajak Y., Smith D.F., Dricka-merK., Weis W.I., TaylorM.E. Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206. J Biol Chem. 2021; 296. doi: 10.1016/j.jbc.2021.100368.
  • PrabhuDas M.R., Baldwin C.L., Bollyky P.L., Bowdish D.M.E., Drickamer K., Febbraio M., Herz J., Kobzik L., Krieger M., Loike J., McVicker B., Means T.K., Moestrup S.K., Post S.R., Sawamura T., Sil-verstein S., Speth R.C., Telfer J.C., Thiele G.M., Wang X.Y., Wright S.D., El Khoury J. A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease. J Immunol. 2017; 198(10): 3775-89. doi: 10.4049/jimmunol.1700373.
Еще
Статья научная
QR-код для установки приложения SciUp Наведите камеру и скачайте бесплатное приложение SciUp