Evaluation of cd44 and Pd-L1 expression during co-cultivation of tumor and hematopoietic stem cells
- Authors: Bykova M.V.1, Aktanova A.A.1,2, Skachkov I.P.1,2, Denisova V.V.3, Pashkina E.A.1,2
-
Affiliations:
- Research Institute of Fundamental and Clinical Immunology
- Novosibirsk State Medical University
- Clinic of Immunopathology, Research Institute of Fundamental and Clinical Immunology
- Issue: Vol 20, No 1 (2025)
- Pages: 122-127
- Section: BASIC RESEARCH
- Published: 21.03.2025
- URL: https://oncohematology.abvpress.ru/ongm/article/view/1011
- DOI: https://doi.org/10.17650/1818-8346-2025-20-1-122-127
- ID: 1011
Cite item
Full Text
Abstract
Background. Cd44 molecule is overexpressed on tumor‑associated cells, including stem cells, in the tumor microenvironment, which in most cases is a poor prognostic marker for the tumor progression. In addition, the pd‑L1 molecule positively correlates with Cd44, which is associated with resistance to antitumor therapy, so these markers are perspective targets for both diagnostics and therapy of oncological diseases.
Aim. To determine the expression of checkpoint molecules and Cd44 during co‑cultivation of tumor and hematopoietic stem cells under various conditions.
Materials and methods. Cd34+ hematopoietic stem cells (n = 10) and tumor lines 1301, K562 and SK‑mel37 were used for this study. Samples labeled with monoclonal antibodies to Cd44, pd‑L1 and pd‑1 were analyzed by flow cytometry.
Results. The expression of molecules was different with co‑culturing of hematopoietic stem cells with several types of tumors, so the number of Cd34+Cd44+ cells was 3 times lower in the group with SK‑mel37 compared to leukemia 1301 and K562 (the median was 7.1; 22.4 and 22.7, respectively). In addition, the expression of the pd‑L1 molecule on SK‑mel37 was significantly higher than on other tumor cells (p < 0.05).
Conclusion. It is necessary to study the patterns of change not only in the expression of these molecules, but also in co‑expression depending on the type and conditions of cells interaction with each other.
About the authors
M. V. Bykova
Research Institute of Fundamental and Clinical Immunology
Author for correspondence.
Email: maria18021997@mail.ru
ORCID iD: 0009-0008-0298-2382
Maria Vladimirovna Bykova
630099; 14 Yadrintsevskaya St.; Novosibirsk
Russian FederationA. A. Aktanova
Research Institute of Fundamental and Clinical Immunology; Novosibirsk State Medical University
ORCID iD: 0000-0002-2075-8551
630099; 14 Yadrintsevskaya St.; 630091; 52 Krasny Prospekt; Novosibirsk
Russian FederationI. P. Skachkov
Research Institute of Fundamental and Clinical Immunology; Novosibirsk State Medical University
ORCID iD: 0009-0000-0530-3818
630099; 14 Yadrintsevskaya St.; 630091; 52 Krasny Prospekt; Novosibirsk
Russian FederationV. V. Denisova
Clinic of Immunopathology, Research Institute of Fundamental and Clinical Immunology
630047; 6 Zalesskogo St.; Novosibirsk
Russian FederationE. A. Pashkina
Research Institute of Fundamental and Clinical Immunology; Novosibirsk State Medical University
ORCID iD: 0000-0002-4912-5512
630099; 14 Yadrintsevskaya St.; 630091; 52 Krasny Prospekt; Novosibirsk
Russian FederationReferences
- Naor D., Sionov R.V., IshShalom D. CD44: structure, function, and association with the malignant process. Adv Cancer Res 1997;71:241–319. doi: 10.1016/s0065230x(08)601013
- Goodison S., Urquidi V., Tarin D. CD44 cell adhesion molecules. Mol Pathol 1999;52(4):189–96. doi: 10.1136/mp.52.4.189
- Jordan A.R., Racine R.R., Hennig M.J., Lokeshwar V.B. The Role of CD44 in disease pathophysiology and targeted treatment. Front Immunol 2015;6:182. doi: 10.3389/fimmu.2015.00182
- Götte M., Yip G.W. Heparanase, hyaluronan, and CD44 in cancers: a breast carcinoma perspective. Cancer Res 2006;66(21):10233–7. doi: 10.1158/00085472.CAN061464
- Cao H., Heazlewood S.Y., Williams B. et al. The role of CD44 in fetal and adult hematopoietic stem cell regulation. Haematologica 2016;101(1):26–37. doi: 10.3324/haematol.2015.135921
- Montgomery N., Hill A., McFarlane S. et al. CD44 enhances invasion of basallike breast cancer cells by upregulating serine protease and collagendegrading enzymatic expression and activity. Breast Cancer Res 2012;14(3):R84. doi: 10.1186/bcr3199
- Makrydimas G., Zagorianakou N., Zagorianakou P., Agnantis N.J. CD44 family and gynaecological cancer. In Vivo 2003;17(6):633–40.
- Zhang S., Wu C.C., Fecteau J.F. et al. Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44. Proc Natl Acad Sci USA 2013;110(15):6127–32. doi: 10.1073/pnas.1221841110
- Zöller M. CD44, hyaluronan, the hematopoietic stem cell, and leukemiainitiating cells. Front Immunol 2015;6:235. doi: 10.3389/fimmu.2015.00235
- Pham P.V., Phan N.L., Nguyen N.T. et al. Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy. J Transl Med 2011;9:209. doi: 10.1186/147958769209
- Kim Ya.S., Kaidina A.M., Chiang J.H. et al. Molecular markers of cancer stem cells verified in vivo. Biomeditsinskaya khimiya = Biomed Khim 2016;62(3):228–38. (In Russ.). doi: 10.18097/PBMC20166203228
- Hanahan D., Coussens L.M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012;21(3):309–22. doi: 10.1016/j.ccr.2012.02.022
- Prieto-Vila M., Takahashi R.U., Usuba W. et al. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci 2017;18(12):2574. doi: 10.3390/ijms18122574
- Lu I.N., Dobersalske C., Rauschenbach L. et al. Tumorassociated hematopoietic stem and progenitor cells positively linked to glioblastoma progression. Nat Commun 2021;12(1):3895. doi: 10.1038/s4146702123995z
- Hendrix M.J., Seftor E.A., Seftor R.E. et al. Reprogramming metastatic tumour cells with embryonic microenvironments. Nat Rev Cancer 2007;7(4):246–55. doi: 10.1038/nrc2108
- Zhao H., Ming T., Tang S. et al. Wnt signaling in colorectal cancer: pathogenic role and therapeutic target. Mol Cancer 2022;21(1):144. doi: 10.1186/s12943022016167
- Greenwald R.J., Freeman G.J., Sharpe A.H. The B7 family revisited. Annu Rev Immunol 2005;23:515–48. doi: 10.1146/annurev.immunol.23.021704.115611
- Dermani F.K., Samadi P., Rahmani G. et al. PD1/PDL1 immune checkpoint: potential target for cancer therapy. J Cell Physiol 2019;234(2):1313–25. doi: 10.1002/jcp.27172
- Ahmadzadeh M., Johnson L.A., Heemskerk B. et al. Tumor antigenspecific CD8 T cells infiltrating the tumor express high levels of PD1 and are functionally impaired. Blood 2009;114(8):1537–44. doi: 10.1182/blood200812195792
- Shi Y. Regulatory mechanisms of PDL1 expression in cancer cells. Cancer Immunol Immunother 2018;67(10):1481–9. doi: 10.1007/s0026201822269
- Cha J.H., Chan L.C., Li C.W. et al. Mechanisms controlling PDL1 expression in cancer. Mol Cell 2019;76(3):359–370. doi: 10.1016/j.molcel.2019.09.030
- Han Y., Liu D., Li L. PD1/PDL1 pathway: current researches in cancer. Am J Cancer Res 2020;10(3):727–42.
- Wang X., Teng F., Kong L., Yu J. PDL1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther 2016;9:5023–39. doi: 10.2147/OTT.S105862
- Wang B., Bai J., Tian B. et al. Genetically engineered hematopoietic stem cells deliver TGFβ inhibitor to enhance bone metastases immunotherapy. Adv Sci (Weinh) 2022;9(28):e2201451. doi: 10.1002/advs.202201451
- Kong T., Ahn R., Yang K. et al. CD44 promotes PDL1 expression and its tumorintrinsic function in breast and lung cancers. Cancer Res 2020;80(3):444–57. doi: 10.1158/00085472.CAN191108
- Zhang C., Wang H., Wang X. et al. CD44, a marker of cancer stem cells, is positively correlated with PDL1 expression and immune cells infiltration in lung adenocarcinoma. Cancer Cell Int 2020;20(1):583. doi: 10.1186/s12935-020-01671-4
Supplementary files

