CCL5 and CCR5 Interaction Promotes Cell Motility in Human Osteosarcoma

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Apr 17

PMID 22506069

Citations 49

Authors

Shih-Wei Wang

Hsing-Hsien Wu

Shih-Chia Liu

Po-Chuan Wang

Wen-Chieh Ou

Wen-Yi Chou

Yung-Shuen Shen

Chih-Hsin Tang

Affiliations

Soon will be listed here.

Abstract

Background: Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES) was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown.

Methodology/principal Findings: Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells.

Conclusions/significance: CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.

Citing Articles

Surface Markers and Chemokines/Cytokines of Tumor-Associated Macrophages in Osteosarcoma and Other Carcinoma Microenviornments-Contradictions and Comparisons.

Tatsuno R, Komohara Y, Pan C, Kawasaki T, Enomoto A, Jubashi T Cancers (Basel). 2024; 16(16).

PMID: 39199574 PMC: 11353089. DOI: 10.3390/cancers16162801.

Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis.

Chang Y, Huang Y, Tsai H, Chang A, Ko C, Fong Y Biomedicines. 2023; 11(10).

PMID: 37893141 PMC: 10604484. DOI: 10.3390/biomedicines11102768.

Analysis of intercellular communication in the osteosarcoma microenvironment based on single cell sequencing data.

Chen F, Liu J, Yang T, Sun J, He X, Fu X J Bone Oncol. 2023; 41:100493.

PMID: 37501717 PMC: 10368934. DOI: 10.1016/j.jbo.2023.100493.

Prostate cancer and bone: clinical presentation and molecular mechanisms.

Wells K, Krackeler M, Jathal M, Parikh M, Ghosh P, Leach J Endocr Relat Cancer. 2023; 30(9).

PMID: 37226936 PMC: 10696925. DOI: 10.1530/ERC-22-0360.

The Chemokines Initiating and Maintaining Immune Hot Phenotype Are Prognostic in ICB of HNSCC.

Huang Y, Liu H, Liu X, Li N, Bai H, Guo C Front Genet. 2022; 13:820065.

PMID: 35692828 PMC: 9186378. DOI: 10.3389/fgene.2022.820065.

References

White D, Kurpios N, Zuo D, Hassell J, Blaess S, Mueller U . Targeted disruption of beta1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction. Cancer Cell. 2004; 6(2):159-70. DOI: 10.1016/j.ccr.2004.06.025. View

Martin L, Blanpain C, Garnier P, Wittamer V, Parmentier M, Vita C . Structural and functional analysis of the RANTES-glycosaminoglycans interactions. Biochemistry. 2001; 40(21):6303-18. DOI: 10.1021/bi002670n. View

Hsieh M, Hsieh C, Lin L, Wu C, Huang G . Differential gene expression of scopolamine-treated rat hippocampus-application of cDNA microarray technology. Life Sci. 2003; 73(8):1007-16. DOI: 10.1016/s0024-3205(03)00372-2. View

Stupack D . The biology of integrins. Oncology (Williston Park). 2007; 21(9 Suppl 3):6-12. View

Tyner J, Uchida O, Kajiwara N, Kim E, Patel A, OSullivan M . CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nat Med. 2005; 11(11):1180-7. PMC: 6322907. DOI: 10.1038/nm1303. View

Schall T, Jongstra J, Dyer B, Jorgensen J, Clayberger C, Davis M . A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988; 141(3):1018-25. View

Takenaka K, Shibuya M, Takeda Y, Hibino S, Gemma A, Ono Y . Altered expression and function of beta1 integrins in a highly metastatic human lung adenocarcinoma cell line. Int J Oncol. 2000; 17(6):1187-94. DOI: 10.3892/ijo.17.6.1187. View

Tseng C, Huang C, Huang C, Cheng J, Stern A, Tseng C . Disabled-2 small interfering RNA modulates cellular adhesive function and MAPK activity during megakaryocytic differentiation of K562 cells. FEBS Lett. 2003; 541(1-3):21-7. DOI: 10.1016/s0014-5793(03)00281-3. View

Arndt C, Crist W . Common musculoskeletal tumors of childhood and adolescence. N Engl J Med. 1999; 341(5):342-52. DOI: 10.1056/NEJM199907293410507. View

10.

Schall T, Bacon K, Toy K, Goeddel D . Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature. 1990; 347(6294):669-71. DOI: 10.1038/347669a0. View

11.

Wang Y, Lee P, Shih C, Chen H, Lee C, Chang Y . Damage formation and repair efficiency in the p53 gene of cell lines and blood lymphocytes assayed by multiplex long quantitative polymerase chain reaction. Anal Biochem. 2003; 319(2):206-15. DOI: 10.1016/s0003-2697(03)00330-0. View

12.

Chuang J, Yang W, Chen H, Huang C, Tan T, Lin Y . CCL5/CCR5 axis promotes the motility of human oral cancer cells. J Cell Physiol. 2009; 220(2):418-26. DOI: 10.1002/jcp.21783. View

13.

Ben-Baruch A . Inflammation-associated immune suppression in cancer: the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol. 2005; 16(1):38-52. DOI: 10.1016/j.semcancer.2005.07.006. View

14.

Kulbe H, Levinson N, Balkwill F, Wilson J . The chemokine network in cancer--much more than directing cell movement. Int J Dev Biol. 2004; 48(5-6):489-96. DOI: 10.1387/ijdb.041814hk. View

15.

Gupta G, Massague J . Cancer metastasis: building a framework. Cell. 2006; 127(4):679-95. DOI: 10.1016/j.cell.2006.11.001. View

16.

Seales E, Jurado G, Brunson B, Wakefield J, Frost A, Bellis S . Hypersialylation of beta1 integrins, observed in colon adenocarcinoma, may contribute to cancer progression by up-regulating cell motility. Cancer Res. 2005; 65(11):4645-52. DOI: 10.1158/0008-5472.CAN-04-3117. View

17.

Luboshits G, Shina S, Kaplan O, Engelberg S, Nass D, Chaitchik S . Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res. 1999; 59(18):4681-7. View

18.

Sliva D . Signaling pathways responsible for cancer cell invasion as targets for cancer therapy. Curr Cancer Drug Targets. 2004; 4(4):327-36. DOI: 10.2174/1568009043332961. View

19.

Yeh W, Lu D, Lee M, Fu W . Leptin induces migration and invasion of glioma cells through MMP-13 production. Glia. 2008; 57(4):454-64. DOI: 10.1002/glia.20773. View

20.

Huang C, Lee C, Chen M, Yang W, Chen Y, Chang C . Stromal cell-derived factor-1/CXCR4 enhanced motility of human osteosarcoma cells involves MEK1/2, ERK and NF-kappaB-dependent pathways. J Cell Physiol. 2009; 221(1):204-12. DOI: 10.1002/jcp.21846. View