Journal of Jilin University(Medicine Edition) ›› 2022, Vol. 48 ›› Issue (2): 374-382.doi: 10.13481/j.1671-587X.20220214

• Research in basic medicine • Previous Articles     Next Articles

Effects of polarization state of tumor-associated macrophages on self-renewal ability and vasculogenic mimicry of prostate cancer stem cells

Ye TIAN(), ABUDU MIJITI·Abudu Kelimu,Peng WANG,Mo SHA,Qi CUI   

  1. Department of Urinary Surgery,Fourth Affiliated Hospital,Xinjiang Medical University,Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine,Urumqi 830000,China
  • Received:2021-05-10 Online:2022-03-28 Published:2022-05-10
  • Contact: Ye TIAN E-mail:barcelonaxj@163.com

Abstract: Objective

To explore the effects of tumor-associated macrophages (TAM) polarization state on the self-renewal ability and vasculogenic mimicry of prostate cancer (Pca) stem cells, and to clarify the effect of TAM in the development of PCa.

Methods

The PCa stem cells were selected from human PCa cell line DU145, and the human mononuclear leukemia cell strain THP-1 was induced into the M2 TAM, which was used as induction group, and the uninduced THP-1 cells were used as control group;real-time fluorescence quantitative PCR(RT-qPCR) method was used to detect the expression levels of inducible nitric oxide synthase (iNOS) mRNA and recombinant human arginase-1 (Arg-1) mRNA in the cells. The experiment was divided into PCa-cancer stem cells(CSC) group (PCa stem cells were cultured in the conventional culture medium), THP-1+PCa-CSC group (PCa stem cells were cultured in the culture supernatant of uninduced THP-1 cells) and TAM+PCa-CSC group (PCa stem cells were cultured in TAM-conditioned medium of induced THP-1 cells); a co-culture system of TAM and PCa stem cells was established by simulating the microenvironment.After 48 h of culture, the spheroidization of PCa stem cells in various groups was detected by cell spheroidization experiment, the number of cell colonies of PCa stem cells in various groups was detected by cell clone formation experiment,cell scratch test was used detect the scratch healing rates of cells in various groups, and Transwell chamber test was used to detect the number of invasion PCa stem cells in various groups; vasculogenic mimicry formation experiment was used to detect the number of tubular structures of PCa stem cells in various groups.

Results

The human PCa DU145 cells were sorted to obtain the CD44+CD133+ labeled prostate cancer stem cells. Compared with control group, the THP-1 cells in induction group showed irregular polygonal shapes, the expression level of iNOS mRNA was decreased (t=21.021, P<0.05), the expression level of Arg-1 mRNA was increased (t=26.153, P<0.05), the expression level of CD86 protein was decreased(t=34.556,P<0.05),and the expression level of CD206 protein was increased(t=31.095,P<0.05). Compared with PCa-CSC group, the volumes of cell spheroids in THP-1+Pca-CSC group and TAM+Pca-CSC group were larger, the number of cell colonies was increased(P<0.05), the scratch healing rates were increased(P<0.05), the number of invasion cells was increased(P<0.05), and the number of tubular structures of cells was also increased(P<0.05). Compared with THP-1+PCa-CSC group, the volume of the cell spheroids in TAM+PCa-CSC group was further increased(P<0.05), the number of cell colonies and the number of invasion cells were increased(P<0.05), the scratch healing rate was increased(P<0.05),and the number of cell tubular structures was increased(P<0.05).

Conclusion

Regulating the polarization state of TAM can induce the metastasis of PCa stem cells, and further promote their self-renewal and vasculogenic mimicry formation.

Key words: Tumor-associated macrophages, Prostate cancer stem cells, Self-renewal, Vasculogenic mimicry

CLC Number: 

  • R737.25