» Articles » PMID: 23335978

Tim-3 Expression in Cervical Cancer Promotes Tumor Metastasis

Overview
Journal PLoS One
Date 2013 Jan 22
PMID 23335978
Citations 81
Authors
Affiliations
Soon will be listed here.
Abstract

Background: T cell immunoglobulin mucin-3 (Tim-3) has been identified as a negative regulator of anti-tumor immunity. Recent studies highlight the important role of Tim-3 in the CD8(+) T cell exhaustion that takes place in both human and animal cancer models. However, the nature of Tim-3 expression in the tumor cell and the mechanism by which it inhibits anti-tumor immunity are unclear. This present study aims to determine Tim-3 is expressed in cervical cancer cells and to evaluate the role of Tim-3 in cervical cancer progression.

Methodology: A total of 85 cervical tissue specimens including 43 human cervical cancer, 22 cervical intraepithelial neoplasia (CIN) and 20 chronic cervicitis were involved. Tim-3 expression in tumor cells was detected and was found to correlate with clinicopathological parameters. Meanwhile, expression of Tim-3 was assessed by RT-PCR, Western Blot and confocal microscopy in cervical cancer cell lines, HeLa and SiHa. The migration and invasion potential of Hela cells was evaluated after inhibiting Tim-3 expression by ADV-antisense Tim-3.

Conclusions: We found that Tim-3 was expressed at a higher level in the clinical cervical cancer cells compared to the CIN and chronic cervicitis controls. We supported this finding by confirming the presence of Tim-3 mRNA and protein in the cervical cell lines. Tim-3 expression in tumor cells correlated with clinicopathological parameters. Patients with high expression of Tim-3 had a significant metastatic potential, advanced cancer grades and shorter overall survival than those with lower expression. Multivariate analysis showed that Tim-3 expression was an independent factor for predicting the prognosis of cervical cancer. Significantly, down-regulating the expression of Tim-3 protein inhibited migration and invasion of Hela cells. Our study suggests that the expression of Tim-3 in tumor cells may be an independent prognostic factor for patients with cervical cancer. Moreover, Tim-3 expression may promote metastatic potential in cervical cancers.

Citing Articles

Retraction: Tim-3 Expression in Cervical Cancer Promotes Tumor Metastasis.

PLoS One. 2024; 19(7):e0308113.

PMID: 39052637 PMC: 11271886. DOI: 10.1371/journal.pone.0308113.


The effects of HIV and oncogenic human papillomavirus on the tumor immune microenvironment of penile squamous cell carcinoma.

Mumba C, Muhimbe Z, Mapulanga V, Kawimbe M, Mutale K, Hamasuku A PLoS One. 2024; 19(5):e0300729.

PMID: 38691575 PMC: 11062539. DOI: 10.1371/journal.pone.0300729.


Promising immunotherapy targets: TIM3, LAG3, and TIGIT joined the party.

Lu C, Tan Y Mol Ther Oncol. 2024; 32(1):200773.

PMID: 38596295 PMC: 10905042. DOI: 10.1016/j.omton.2024.200773.


CircPVT1 promotes migration and invasion by regulating miR-490-5p/HAVCR2 axis in osteosarcoma cells.

Zhou C, Balmer L, Song M, Wu K, Wang W, Wang H J Cell Mol Med. 2024; 28(8):e18269.

PMID: 38568056 PMC: 10989635. DOI: 10.1111/jcmm.18269.


Pan-cancer analysis of TIM-3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity.

Lim J, Kurzrock R, Nishizaki D, Miyashita H, Adashek J, Lee S Cancer Med. 2023; 13(1):e6844.

PMID: 38132831 PMC: 10807558. DOI: 10.1002/cam4.6844.


References
1.
Sakuishi K, Jayaraman P, Behar S, Anderson A, Kuchroo V . Emerging Tim-3 functions in antimicrobial and tumor immunity. Trends Immunol. 2011; 32(8):345-9. PMC: 3164311. DOI: 10.1016/j.it.2011.05.003. View

2.
Zhou Q, Munger M, Veenstra R, Weigel B, Hirashima M, Munn D . Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011; 117(17):4501-10. PMC: 3099570. DOI: 10.1182/blood-2010-10-310425. View

3.
Kloth J, Gorter A, Fleuren G, Oosting J, Uljee S, Ter Haar N . Elevated expression of SerpinA1 and SerpinA3 in HLA-positive cervical carcinoma. J Pathol. 2008; 215(3):222-30. DOI: 10.1002/path.2347. View

4.
Huang X, Bai X, Cao Y, Wu J, Huang M, Tang D . Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion. J Exp Med. 2010; 207(3):505-20. PMC: 2839144. DOI: 10.1084/jem.20090397. View

5.
Alderton G . Metastasis. Exosomes drive premetastatic niche formation. Nat Rev Cancer. 2012; 12(7):447. DOI: 10.1038/nrc3304. View