ShRNA Knock-down of CXCR7 Inhibits Tumour Invasion and Metastasis in Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2017 Apr 22

PMID 28429395

Citations 10

Authors

Zhong-Wei Zhao

Xiao-Xi Fan

Jing-Jing Song

Min Xu

Min-Jiang Chen

Jian-Fei Tu

Fa-Zong Wu

Deng-Ke Zhang

Lu Liu

Li Chen

Xi-Hui Ying

Jian-Song Ji

Affiliations

Soon will be listed here.

Abstract

To investigate the effects of lentiviral vector-mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7-shRNA, negative control (NC) and blank groups. The qRT-PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP-2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC was established. Fifty model rats were divided into the CXCR7-shRNA + TACE, CXCR7-shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect the expressions of CXCR7, MMP-2, vascular endothelial growth factor (VEGF) and intratumoral CD31-positive vessel count in tumour tissues of mice. Compared with the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP-2 were decreased in the CXCR7-shRNA group. The cell proliferation and invasion rates of the CXCR7-shRNA group were lower than the blank and NC groups. At the 4th week after TACE, tumour weight of the CXCR7-shRNA + TACE group increased continuously. The CXCR7-shRNA + TACE group showed longer survival time and smaller tumour sizes than other groups. Compared with other groups, the CXCR7-shRNA + TACE and CXCR7-shRNA groups had less number of lung metastatic nodules and lower expressions of CXCR7, MMP-2, VEGF and CD31-positive vessel count. CXCR7-shRNA inhibits tumour invasion and metastasis to improve the efficacy of TACE in HCC by reducing the expressions of CXCR7, MMP-2 and VEGF.

Citing Articles

CXCR7 promotes pulmonary vascular remodeling via targeting p38/MMP2 pathway in pulmonary arterial hypertension.

Xu J, Miao S, Wu T, Hu C, Huang D, Zhang X J Thorac Dis. 2024; 16(4):2460-2471.

PMID: 38738224 PMC: 11087638. DOI: 10.21037/jtd-24-331.

Interventional Radiology Image-Guided Locoregional Therapies (LRTs) and Immunotherapy for the Treatment of HCC.

Biondetti P, Saggiante L, Ierardi A, Iavarone M, Sangiovanni A, Pesapane F Cancers (Basel). 2021; 13(22).

PMID: 34830949 PMC: 8616392. DOI: 10.3390/cancers13225797.

Emerging Importance of Chemokine Receptor CXCR4 and Its Ligand in Liver Disease.

Wang S, Gao S, Li Y, Qian X, Luan J, Lv X Front Cell Dev Biol. 2021; 9:716842.

PMID: 34386499 PMC: 8353181. DOI: 10.3389/fcell.2021.716842.

CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies.

Khare T, Bissonnette M, Khare S Int J Mol Sci. 2021; 22(14).

PMID: 34298991 PMC: 8305488. DOI: 10.3390/ijms22147371.

Use of signals of positive and negative selection to distinguish cancer genes and passenger genes.

Banyai L, Trexler M, Kerekes K, Csuka O, Patthy L Elife. 2021; 10.

PMID: 33427197 PMC: 7877913. DOI: 10.7554/eLife.59629.

References

Salazar N, Munoz D, Hoy J, Lokeshwar B . Use of shRNA for stable suppression of chemokine receptor expression and function in human cancer cell lines. Methods Mol Biol. 2014; 1172:209-18. PMC: 4236910. DOI: 10.1007/978-1-4939-0928-5_19. View

Decock J, Thirkettle S, Wagstaff L, Edwards D . Matrix metalloproteinases: protective roles in cancer. J Cell Mol Med. 2011; 15(6):1254-65. PMC: 4373327. DOI: 10.1111/j.1582-4934.2011.01302.x. View

Miao Z, Luker K, Summers B, Berahovich R, Bhojani M, Rehemtulla A . CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci U S A. 2007; 104(40):15735-40. PMC: 1994579. DOI: 10.1073/pnas.0610444104. View

. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 385(9963):117-71. PMC: 4340604. DOI: 10.1016/S0140-6736(14)61682-2. View

Xue T, Chen R, Han D, Chen J, Xue Q, Gao D . Down-regulation of CXCR7 inhibits the growth and lung metastasis of human hepatocellular carcinoma cells with highly metastatic potential. Exp Ther Med. 2012; 3(1):117-123. PMC: 3438632. DOI: 10.3892/etm.2011.358. View

Zheng K, Li H, Su X, Wang X, Tian T, Li F . Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2010; 29:31. PMC: 2859378. DOI: 10.1186/1756-9966-29-31. View

Xue T, Han D, Chen R, Zou J, Wang Y, Tang Z . High expression of CXCR7 combined with Alpha fetoprotein in hepatocellular carcinoma correlates with extra-hepatic metastasis to lung after hepatectomy. Asian Pac J Cancer Prev. 2011; 12(3):657-63. View

Nordenstedt H, White D, El-Serag H . The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis. 2010; 42 Suppl 3:S206-14. PMC: 3392755. DOI: 10.1016/S1590-8658(10)60507-5. View

Neve Polimeno M, Ierano C, DAlterio C, Losito N, Napolitano M, Portella L . CXCR4 expression affects overall survival of HCC patients whereas CXCR7 expression does not. Cell Mol Immunol. 2014; 12(4):474-82. PMC: 4496532. DOI: 10.1038/cmi.2014.102. View

10.

Zlotnik A . Chemokines and cancer. Int J Cancer. 2006; 119(9):2026-9. DOI: 10.1002/ijc.22024. View

11.

Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta K . The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem. 2007; 283(7):4283-94. DOI: 10.1074/jbc.M707465200. View

12.

Zabel B, Miao Z, Lai N, Wang Y, Lewen S, Berahovich R . CXCR7 protein expression correlates with elevated mmp-3 secretion in breast cancer cells. Oncol Lett. 2012; 1(5):845-847. PMC: 3436257. DOI: 10.3892/ol_00000149. View

13.

Sergio A, Cristofori C, Cardin R, Pivetta G, Ragazzi R, Baldan A . Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol. 2008; 103(4):914-21. DOI: 10.1111/j.1572-0241.2007.01712.x. View

14.

Chen Q, Cheng C, Chen H, Ning Z, Tang S, Zhang X . Effectiveness and complications of ultrasound guided fine needle aspiration for primary liver cancer in a Chinese population with serum α-fetoprotein levels ≤200 ng/ml--a study based on 4,312 patients. PLoS One. 2014; 9(8):e101536. PMC: 4149350. DOI: 10.1371/journal.pone.0101536. View

15.

Ben-Baruch A . Organ selectivity in metastasis: regulation by chemokines and their receptors. Clin Exp Metastasis. 2007; 25(4):345-56. DOI: 10.1007/s10585-007-9097-3. View

16.

Lencioni R, Chen X, Dagher L, Venook A . Treatment of intermediate/advanced hepatocellular carcinoma in the clinic: how can outcomes be improved?. Oncologist. 2010; 15 Suppl 4:42-52. DOI: 10.1634/theoncologist.2010-S4-42. View

17.

Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K . Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer. 2010; 116(23):5452-60. DOI: 10.1002/cncr.25314. View

18.

Koizumi K, Hojo S, Akashi T, Yasumoto K, Saiki I . Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response. Cancer Sci. 2007; 98(11):1652-8. PMC: 11159633. DOI: 10.1111/j.1349-7006.2007.00606.x. View

19.

Burrel M, Reig M, Forner A, Barrufet M, Rodriguez de Lope C, Tremosini S . Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design. J Hepatol. 2012; 56(6):1330-5. DOI: 10.1016/j.jhep.2012.01.008. View

20.

Kim D, Ryu H, Choi J, Park J, Lee D, Kim B . Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma. Aliment Pharmacol Ther. 2012; 35(11):1343-50. DOI: 10.1111/j.1365-2036.2012.05089.x. View