Relationship between CD 163 Tumor-Associated Macrophages and Colorectal-Cancer Stem Cell Markers

Authors

  • Imelda Rey Department of Internal Medicine, Medical Faculty, Universitas Sumatera Utara, 2015 Medan, Indonesia
  • Agung Putra Stem Cell And Cancer Research, Medical Faculty, Sultan Agung Islamic University (UNISSULA), 50112 Semarang, Indonesia; Doctoral Department of Medicine Science, Medical Faculty, Universitas Sumatera Utara, 20155 Medan, Indonesia; Department of Pathology Anatomy, Medical Faculty, Sultan Agung Islamic University (UNISSULA), 50112 Semarang, Indonesia
  • Dharma Lindarto Department of Internal Medicine, Medical Faculty, Universitas Sumatera Utara, 2015 Medan, Indonesia; Doctoral Department of Medicine Science, Medical Faculty, Universitas Sumatera Utara, 20155 Medan, Indonesia
  • Fauzi Yusuf Department of Medicine Science, Medical Faculty, Universitas Sumatera Utara, 20155 Medan, Indonesia; Department of Internal Medicine, Medical Faculty, Syiah Kuala Univeristy, 23111 Banda Aceh, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7188

Keywords:

CD163, Tumor-associated macrophage, CD133, CD166, Colorectal-cancer stem cells

Abstract

BACKGROUND: Colorectal-cancer stem cells (CR-CSCs) represent a specific subpopulation of colorectal cancer (CRC) cells, which are characterized by the expression of CD133 and CD166. Tumor-associated macrophages (TAMs), found near CSCs may represent polarized macrophages, which are characterized by CD163 expression. In most tumors, TAMs may promote aggressive tumor development, leading to poor prognoses.

AIM: The aim of this study was to determine whether any association exists between CD163 expression in TAMs and CD133 and CD166 expression in CR-CSCs.

METHODS: This study used a cross-sectional design that was conducted at the General Hospital and affiliates in Medan, from September 2018 to July 2019. CRC tissues were collected from colonoscopy biopsies and surgical resections performed on CRC patients, who fulfilled all necessary inclusion and exclusion criteria and provided informed consent. Subjects were divided into high- and low-CD163-level groups. We analyzed the expression levels of CD163, CD133, and CD166 using immunohistochemical (IHC) assays.

RESULTS: A total of 118 CRC patients were enrolled in this study, of whom 58.5% were male. No significant differences in hemoglobin, leukocyte, or platelet levels were observed between high- and low-level CD163 expression. We didn’t find any significant association of CD163 TAM with CRC histological grade and TNM stagings. Significant associations were found between the CD 163 expression level and the CD133 expression level (p < 0.001) and between the CD 163 expression level and the CD166 expression level (p< 0.001). Increased TAM levels of CD163 was associated with 2.770-fold and 2.616-fold increased risks of elevated CD133 and CD166 levels, respectively.

CONCLUSION: An association was found between the expression levels of CD163 in TAMs and the expression levels of CD133 and CD166 in CR-CSCs.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Granados-Romero JJ, Valderrama-Treviño AI, Contreras- Flores EH, Barrera-Mera B, Enríquez MH, Uriarte-Ruíz K, et al. Colorectal cancer: A review. Int J Res Med Sci. 2017;5(11):4667-76. http://doi.org/10.3390/ijms18010197 PMid:28106826 DOI: https://doi.org/10.18203/2320-6012.ijrms20174914

Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2015;65(1):5-29. http://doi.org/10.3322/caac.21254 PMid:25559415 DOI: https://doi.org/10.3322/caac.21254

Prieto-vila M, Takahashi R, Usuba W, Kohama I, Ochiya T. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci. 2017;18(12):2574. http://doi.org/10.3390/ijms18122574 PMid:29194401 DOI: https://doi.org/10.3390/ijms18122574

Hammond WA, Swaika A, Mody K. Pharmacologic resistance in colorectal cancer: A review. The Adv Med Oncol Rev. 2016;8(1):57-84. http://doi.org/10.1177/1758834015614530 PMid:26753006 DOI: https://doi.org/10.1177/1758834015614530

Humphries HN, Wickremesekera SK, Marsh RW, Brasch HD, Mehrotra S, Tan ST, et al. Characterization of cancer stem cells in colon adenocarcinoma metastasis to the liver. Front Surg. 2018;4:1-76. http://doi.org/10.3389/fsurg.2017.00076 PMid:29404335 DOI: https://doi.org/10.3389/fsurg.2017.00076

Wang J, Li D, Cang H, Guo B. Crosstalk between cancer and immune cells: Role of tumor associated macrophages in the tumor microenvironment. Cancer Med. 2019;8:4709-21. http://doi.org/10.1002/cam4.2327 PMid:31222971 DOI: https://doi.org/10.1002/cam4.2327

Liu J, Peng C, Yang G, Hu W, Yang X. Distribution pattern of tumor associated macrophages predicts the prognosis of gastric cancer. Oncotarget. 2017;8(54):92757-69. http://doi.org/10.18632/oncotarget.21575 PMid:29190953 DOI: https://doi.org/10.18632/oncotarget.21575

Irjala H, Vaittinen S, Huhtinen H, Sundstro J, Salmi M, Ristama R. Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients. Int J Cancer Type. 2012;873:864-73. http://doi.org/10.1002/ijc.26457 PMid:21952788 DOI: https://doi.org/10.1002/ijc.26457

Pinto ML, Rios E, Durães C, Ribeiro R. The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Front Immunol. 2019;10:1875. http://doi.org/10.3389/fimmu.2019.01875 PMid:31481956 DOI: https://doi.org/10.3389/fimmu.2019.01875

Biswas SK, Mantovani A. Review Macrophage plasticity and interaction with lymphocyte subsets : Cancer as a paradigm. Nat Immunol. 2010;11(10):889-96. http://doi.org/10.1038/ni.1937 PMid:20856220 DOI: https://doi.org/10.1038/ni.1937

Qian B, Pollard JW. Review macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39-51. http://doi.org/10.1016/j.cell.2010.03.014 PMid:20371344 DOI: https://doi.org/10.1016/j.cell.2010.03.014

Larionova I, Cherdyntseva N, Liu T. Interaction of tumor-associated macrophages and cancer chemotherapy. Oncoimmunology. 2019;8(7):1596004. http://doi.org/10.1080/2162402X.2019.1596004 PMid:31143517 DOI: https://doi.org/10.1080/2162402X.2019.1596004

Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: Biological roles and clinical therapeutic applications. J Hematol Oncol. 2019;3:76. http://doi.org/10.1186/s13045-019-0760-3 PMid:31300030 DOI: https://doi.org/10.1186/s13045-019-0760-3

Zhang Q, Liu L, Gong C, Shi H, Zeng Y, Wang X. Prognostic significance of tumor-associated macrophages in solid tumor: A meta-analysis of the literature. PLoS One. 2012;7(12):e50946. http://doi.org/10.1371/journal.pone.0050946 PMid:23284651 DOI: https://doi.org/10.1371/journal.pone.0050946

Horst D, Kriegl L, Engel J, Kirchner T, Jung A. Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. Cancer Invest. 2009;27(8):844-50. http://doi.org/10.1080/07357900902744502 PMid:19626493 DOI: https://doi.org/10.1080/07357900902744502

Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, et al. Prognostic impact of the expression of putative cancer stem cell colorectal cancer. Br J Cancer. 2010;103(3):382-90. http://doi.org/10.1038/sj.bjc.6605762 PMid:20606680 DOI: https://doi.org/10.1038/sj.bjc.6605762

Hansen AG, Freeman TJ, Arnold SA, Starchenko A, Jones-paris CR, Gilger MA, et al. Elevated ALCAM shedding in colorectal cancer correlates with poor patient outcome. Cancer Res. 2013;(9):2955-65. http://doi.org/10.1158/0008-5472.CAN-12-2052 PMid:23539446 DOI: https://doi.org/10.1158/0008-5472.CAN-12-2052

Li X, Bu W, Meng L, Liu X, Wang S, Jiang L. CXCL12/CXCR4 pathway orchestrates CSC-like properties by CAF recruited tumor associated macrophage in OSCC. Exp Cell Res. 2019;378(2):131-8. http://doi.org/10.1016/j.yexcr.2019.03.013 PMid:30857971 DOI: https://doi.org/10.1016/j.yexcr.2019.03.013

Plaks V, Kong N, Werb Z. Perspective the cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 2015;16(3):225-38. http://doi.org/10.1016/j.stem.2015.02.015 PMid:25748930 DOI: https://doi.org/10.1016/j.stem.2015.02.015

Kato Y, Nishihara H, Mohri H, Kanno H, Kobayashi H. Clinicopathological evaluation of cyclooxygenase-2 expression in meningioma: Immunohistochemical analysis of 76 cases of low and high-grade meningioma. Brain Tumor Pathol. 2014;31(1):23-30. http://doi.org/10.1007/s10014-012-0127-8 PMid:23250387 DOI: https://doi.org/10.1007/s10014-012-0127-8

Raggi C, Mousa HS, Correnti M, Sica A, Invernizzi P. Cancer stem cells and tumor-associated macrophages: A roadmap for multitargeting strategies. Oncogene. 2015;35(6):671-82. http://doi.org/10.1038/onc.2015.132 PMid:25961921 DOI: https://doi.org/10.1038/onc.2015.132

Caronni N, Savino B, Bonecchi R. Immunobiology Myeloid cells in cancer-related inflammation. Immunobiology. 2015;220(2):249-53. http://doi.org/10.1016/j.imbio.2014.10.001 PMid:25454487 DOI: https://doi.org/10.1016/j.imbio.2014.10.001

Kazama S, Kishikawa J, Kiyomatsu T, Kawai K, Nozawa H, Ishihara S. Expression of the stem cell marker CD133 is related to tumor development in colorectal carcinogenesis. Asian J Surg. 2018;41(3):274-8. http://doi.org/10.1016/j.asjsur.2016.12.002 PMid:28190751 DOI: https://doi.org/10.1016/j.asjsur.2016.12.002

Corbeil D, Marzesco A, Wilsch-bräuninger M, Huttner WB. The intriguing links between prominin-1 (CD133), cholesterol-based membrane microdomains, remodeling of apical plasma membrane protrusions, extracellular membrane particles, and (neuro) epithelial cell differentiation. FEBS Lett. 2010;584(9):1659-64. PMid:20122930 DOI: https://doi.org/10.1016/j.febslet.2010.01.050

Smith NR, Davies PS, Levin TG, Gallagher AC, Keene DR, Sengupta SK, et al. Cell adhesion molecule CD166/ALCAM functions within the crypt to orchestrate murine intestinal stem cell homeostasis. Cell Mol Gastroenterol Hepatol. 2016;3(3):389-409. http://doi.org/10.1016/j.jcmgh.2016.12.010 PMid:28462380 DOI: https://doi.org/10.1016/j.jcmgh.2016.12.010

Maniecki MB, Etzerodt A, Ulhøi BP, Steiniche T, Borre M, Dyrskjøt L, et al. Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells. Int J Cancer. 2012;131(10):2320-31. http://doi.org/10.1002/ijc.27506 PMid:22362417 DOI: https://doi.org/10.1002/ijc.27506

Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 2018;25(20):1-18. http://doi.org/10.1186/s12929-018-0426-4 PMid:29506506 DOI: https://doi.org/10.1186/s12929-018-0426-4

Owen JL, Mohamadzadeh M. Macrophages and chemokines as mediators of angiogenesis. Front Physiol. 2013;4:159. http://doi.org/10.3389/fphys.2013.00159 PMid:23847541 DOI: https://doi.org/10.3389/fphys.2013.00159

Guo Q, Jin Z, Yuan Y, Liu R, Xu T, Wei H, et al. New mechanisms of tumor-associated macrophages on promoting tumor progression: Recent research advances and potential targets for tumor immunotherapy. J Immunol Res. 2016;2016:9720912. http://doi.org/10.1155/2016/9720912 PMid:27975071 DOI: https://doi.org/10.1155/2016/9720912

Fan F, Wang R, Boulbes DR, Zhang H, Watowich SS, Xia L, et al. Macrophage conditioned medium promotes colorectal cancer stem cell phenotype via the hedgehog signaling pathway. PLoS One. 2018;13(1):e0190070. http://doi.org/10.1371/journal.pone.0190070 PMid:29293549 DOI: https://doi.org/10.1371/journal.pone.0190070

Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci U S A. 2011;108(30):12425-30. http://doi.org/10.1073/pnas.1106645108 PMid:21746895 DOI: https://doi.org/10.1073/pnas.1106645108

Zhou Q, Peng R, Wu X, Xia Q, Hou J, Ding Y, et al. The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer. J Transl Med. 2010;8(13):1-9. http://doi.org/10.1186/1479-5876-8-13 PMid:20141634 DOI: https://doi.org/10.1186/1479-5876-8-13

Henze A, Mazzone M. The impact of hypoxia on tumor-associated macrophages. J Clin Invest. 2016;126(10):3672-9. http://doi.org/10.1172/JCI84427 PMid:27482883 DOI: https://doi.org/10.1172/JCI84427

Chen Y, Tan W, Wang C. Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial mesenchymal transition. Onco Targets Ther. 2018;11:3817-26. http://doi.org/10.2147/OTT.S168317 PMid:30013362 DOI: https://doi.org/10.2147/OTT.S168317

Hanahan D, Weinberg RA. Biological hallmarks of cancer. In: Bast RC, Croce CM, Hait WN, Hong WK, Kufe DW, Piccart- Gebhrart M, editors. Holland-Frei Cancer Medicine. 9th ed. Hoboken, New Jersey: John Wiley & Sons, Inc.;2017. p. 1-10.

Ruslie RH, Darmadi D. Administration of neem (Azadirachta indica A. Juss) leaf extract decreases TNF-a and IL-6 expressions in dextran sodium sulfate-induced colitis in rats. J Adv Vet Anim Res. 2020;7:744-9. http://doi.org/10.5455/javar.2020.g476 PMid:33409321 DOI: https://doi.org/10.5455/javar.2020.g476

Ruslie RH, Darmadi D, Siregar GA. The effect of neem (Azadirachta indica) leaf extracts on interleukin-10 expression and histological score in dextran sodium sulfate-induced colitis mice. Open Access Maced J Med Sci. 2020;8:578-82. DOI: https://doi.org/10.3889/oamjms.2020.4809

Oosterling SJ, van der Bij GJ, Meijer GA, Tuk CW, Garderen E, van Rooijen N, et al. Macrophages direct tumour histology and clinicaloutcome in a colon cancer model. J Pathol. 2005;207(2):147-55. http://doi.org/10.1002/path.1830 PMid:16104052 DOI: https://doi.org/10.1002/path.1830

Tan SY, Fan Y, Luo HS, Shen ZX, Guo Y, Zhao LJ. Prognostic significance of cell infiltrations of immunosurveillance in colorectal cancer. World J Gastroenterol. 2005;11(8):1210-4. http://doi.org/10.3748/wjg.v11.i8.1210 PMid:15754407 DOI: https://doi.org/10.3748/wjg.v11.i8.1210

Forssell J, Oberg A, Henriksson ML, Senling R, Jung A, Palmqvist R. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res. 2007;13(5):1472-9. http://doi.org/10.1158/1078-0432.CCR-06-2073 PMid:17332291 DOI: https://doi.org/10.1158/1078-0432.CCR-06-2073

Bacman D, Merkel S, Croner R, Papadopoulos T, Brueckl W, et al. TGFbeta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: A retrospective study. BMC Cancer. 2007;7:156. http://doi.org/10.1186/1471-2407-7-156 PMid:17692120 DOI: https://doi.org/10.1186/1471-2407-7-156

Koelzera VH, Canonica K, Dawsona H, Sokol L, Karamitopoulou-Diamantisa E, Luglia A, et al. Phenotyping of tumor-associated macrophages in colorectal cancer: Impact on single cell invasion (tumor budding) and clinicopathological outcome. Oncoimmunology. 2016;5(4):e1106677. http://doi.org/10.1080/2162402X.2015.1106677 PMid:27141391 DOI: https://doi.org/10.1080/2162402X.2015.1106677

Khorana AA, Ryan CK, Cox C, Eberly S, Sahasrabudhe DM. Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with Stage II and Stage III colon carcinoma: A role for the host response in prognosis. Cancer. 2003;97(4):960-8. http://doi.org/10.1002/cncr.11152 PMid:12569594 DOI: https://doi.org/10.1002/cncr.11152

Downloads

Published

2021-10-19

How to Cite

1.
Rey I, Putra A, Lindarto D, Yusuf F. Relationship between CD 163 Tumor-Associated Macrophages and Colorectal-Cancer Stem Cell Markers. Open Access Maced J Med Sci [Internet]. 2021 Oct. 19 [cited 2024 Nov. 21];9(B):1381-6. Available from: https://oamjms.eu/index.php/mjms/article/view/7188