In Vitro Co-Culture Models of Breast Cancer Metastatic Progression Towards Bone

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 Aug 30

PMID 27571063

Citations 17

Authors

Chiara Arrigoni

Simone Bersini

Mara Gilardi

Matteo Moretti

Affiliations

Soon will be listed here.

Abstract

Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps.

Citing Articles

Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.

Feng Q, Shan X, Yau V, Cai Z, Xie S Pharmaceuticals (Basel). 2025; 18(1).

PMID: 39861125 PMC: 11769033. DOI: 10.3390/ph18010062.

Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model.

Moghimi N, Hosseini S, Dalan A, Mohammadrezaei D, Goldman A, Kohandel M Sci Rep. 2023; 13(1):13648.

PMID: 37607994 PMC: 10444838. DOI: 10.1038/s41598-023-40680-x.

Co-targeting triple-negative breast cancer cells and endothelial cells by metronomic chemotherapy inhibits cell regrowth and migration downregulation of the FAK/VEGFR2/VEGF axis and autophagy/apoptosis activation.

Scagliotti A, Capizzi L, Cazzaniga M, Ilari A, De Giorgi M, Cordani N Front Oncol. 2022; 12:998274.

PMID: 36531071 PMC: 9749857. DOI: 10.3389/fonc.2022.998274.

Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies.

Bernardin A, Colombani S, Rousselot A, Andry V, Goumon Y, Delanoe-Ayari H Cells. 2022; 11(23).

PMID: 36497024 PMC: 9737466. DOI: 10.3390/cells11233764.

Fadu head and neck squamous cell carcinoma induces hyperexcitability of primary sensory neurons in an in vitro coculture model.

Uhelski M, Gorur A, Shi T, Corrales G, Du K, Li Y Pain Rep. 2022; 7(3):e1012.

PMID: 35620249 PMC: 9113206. DOI: 10.1097/PR9.0000000000001012.

References

Cooper C, Sikes R, Nicholson B, Sun Y, Pienta K, Taichman R . Cancer cells homing to bone: the significance of chemotaxis and cell adhesion. Cancer Treat Res. 2004; 118:291-309. DOI: 10.1007/978-1-4419-9129-4_12. View

Lim P, Bliss S, Patel S, Taborga M, Dave M, Gregory L . Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells. Cancer Res. 2011; 71(5):1550-60. DOI: 10.1158/0008-5472.CAN-10-2372. View

Shalhoub V, Faust J, Boyle W, Dunstan C, Kelley M, Kaufman S . Osteoprotegerin and osteoprotegerin ligand effects on osteoclast formation from human peripheral blood mononuclear cell precursors. J Cell Biochem. 1999; 72(2):251-61. View

Bongio M, Lopa S, Gilardi M, Bersini S, Moretti M . A 3D vascularized bone remodeling model combining osteoblasts and osteoclasts in a CaP nanoparticle-enriched matrix. Nanomedicine (Lond). 2016; 11(9):1073-91. DOI: 10.2217/nnm-2015-0021. View

Coleman R . Skeletal complications of malignancy. Cancer. 1997; 80(8 Suppl):1588-94. DOI: 10.1002/(sici)1097-0142(19971015)80:8+<1588::aid-cncr9>3.3.co;2-z. View

Reymond N, Borda DAgua B, Ridley A . Crossing the endothelial barrier during metastasis. Nat Rev Cancer. 2013; 13(12):858-70. DOI: 10.1038/nrc3628. View

Sosnoski D, Norgard R, Grove C, Foster S, Mastro A . Dormancy and growth of metastatic breast cancer cells in a bone-like microenvironment. Clin Exp Metastasis. 2015; 32(4):335-44. DOI: 10.1007/s10585-015-9710-9. View

Ghajar C, Peinado H, Mori H, Matei I, Evason K, Brazier H . The perivascular niche regulates breast tumour dormancy. Nat Cell Biol. 2013; 15(7):807-17. PMC: 3826912. DOI: 10.1038/ncb2767. View

Varani K, Vincenzi F, Targa M, Paradiso B, Parrilli A, Fini M . The stimulation of A(3) adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. Eur J Cancer. 2012; 49(2):482-91. DOI: 10.1016/j.ejca.2012.06.005. View

10.

Taubenberger A . In vitro microenvironments to study breast cancer bone colonisation. Adv Drug Deliv Rev. 2014; 79-80:135-44. DOI: 10.1016/j.addr.2014.10.014. View

11.

Spiegel A, Brooks M, Houshyar S, Reinhardt F, Ardolino M, Fessler E . Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells. Cancer Discov. 2016; 6(6):630-49. PMC: 4918202. DOI: 10.1158/2159-8290.CD-15-1157. View

12.

Bersini S, Gilardi M, Arrigoni C, Talo G, Zamai M, Zagra L . Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach. Biomaterials. 2015; 76:157-72. DOI: 10.1016/j.biomaterials.2015.10.057. View

13.

Chaffer C, Weinberg R . A perspective on cancer cell metastasis. Science. 2011; 331(6024):1559-64. DOI: 10.1126/science.1203543. View

14.

Marlow R, Honeth G, Lombardi S, Cariati M, Hessey S, Pipili A . A novel model of dormancy for bone metastatic breast cancer cells. Cancer Res. 2013; 73(23):6886-99. DOI: 10.1158/0008-5472.CAN-13-0991. View

15.

Oskarsson T, Massague J . Extracellular matrix players in metastatic niches. EMBO J. 2011; 31(2):254-6. PMC: 3261570. DOI: 10.1038/emboj.2011.469. View

16.

Zhang Z, Wang H, Ikeda S, Fahey F, Bielenberg D, Smits P . Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis. Am J Pathol. 2010; 177(3):1459-69. PMC: 2928977. DOI: 10.2353/ajpath.2010.090476. View

17.

Wang H, Yu C, Gao X, Welte T, Muscarella A, Tian L . The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. Cancer Cell. 2015; 27(2):193-210. PMC: 4326554. DOI: 10.1016/j.ccell.2014.11.017. View

18.

Chen Y, Shi H, Stock S, Stern P, Zhang M . Regulation of breast cancer-induced bone lesions by β-catenin protein signaling. J Biol Chem. 2011; 286(49):42575-42584. PMC: 3234960. DOI: 10.1074/jbc.M111.294595. View

19.

Wang J, Jarrett J, Huang C, Satcher Jr R, Levenson A . Identification of estrogen-responsive genes involved in breast cancer metastases to the bone. Clin Exp Metastasis. 2007; 24(6):411-22. DOI: 10.1007/s10585-007-9078-6. View

20.

Chen Y, Sosnoski D, Mastro A . Breast cancer metastasis to the bone: mechanisms of bone loss. Breast Cancer Res. 2010; 12(6):215. PMC: 3046443. DOI: 10.1186/bcr2781. View