Evaluation of cd44 and Pd-L1 expression during co-cultivation of tumor and hematopoietic stem cells

Cover Page

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 Federation

A. 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 Federation

I. 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 Federation

V. V. Denisova

Clinic of Immunopathology, Research Institute of Fundamental and Clinical Immunology

630047; 6 Zalesskogo St.; Novosibirsk

Russian Federation

E. 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 Federation

References

  1. 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
  2. Goodison S., Urquidi V., Tarin D. CD44 cell adhesion molecules. Mol Pathol 1999;52(4):189–96. doi: 10.1136/mp.52.4.189
  3. 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
  4. 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
  5. 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
  6. 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
  7. Makrydimas G., Zagorianakou N., Zagorianakou P., Agnantis N.J. CD44 family and gynaecological cancer. In Vivo 2003;17(6):633–40.
  8. 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
  9. Zöller M. CD44, hyaluronan, the hematopoietic stem cell, and leukemia­initiating cells. Front Immunol 2015;6:235. doi: 10.3389/fimmu.2015.00235
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. Shi Y. Regulatory mechanisms of PD­L1 expression in cancer cells. Cancer Immunol Immunother 2018;67(10):1481–9. doi: 10.1007/s00262­018­2226­9
  21. 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
  22. Han Y., Liu D., Li L. PD­1/PD­L1 pathway: current researches in cancer. Am J Cancer Res 2020;10(3):727–42.
  23. 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
  24. 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
  25. 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
  26. 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

Supplementary Files
Action
1. JATS XML

Copyright (c)



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-36928 от  21.07.2009.