Similar articles

Abstract: breast cancer is the most common cancer in women and one of the deadliest cancers worldwide. According to the distribution of tumor tissue, breast cancer can be divided into invasive and non-invasive forms. The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body, forming metastatic breast cancer. Drug resistance and distant metastasis are the main causes of death from breast cancer. Research on breast cancer has attracted extensive attention from researchers. In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening. The tumor microenvironment consists of cancer cells and various types of stromal cells, including fibroblasts, endothelial cells, mesenchymal cells, and immune cells embedded in the extracellular matrix. The extracellular matrix contains fibrin proteins (such as types I, II, III, IV, VI, and X collagen and elastin) and glycoproteins (such as proteoglycan, laminin, and fibronectin), which are involved in cell signaling and binding of growth factors. The current traditional two-dimensional (2D) tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo. Therefore, in recent years, research on three-dimensional (3D) tumor models has gradually increased, especially 3D bioprinting models with high precision and repeatability. Compared with a 2D model, the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment. Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments. Acellular matrix, gelatin, sodium alginate, and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection. Here, we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models, as a reference for research in the field of breast cancer.

基于天然水凝胶的三维乳腺癌肿瘤模型研究进展

[1]AlmendroV, FusterG, 2011. Heterogeneity of breast cancer: etiology and clinical relevance. Clin Transl Oncol, 13(11):767-773.

[2]AungA, TheprungsirikulJ, LimHL, et al., 2016. Chemotaxis-driven assembly of endothelial barrier in a tumor-on-a-chip platform. Lab Chip, 16(10):1886-1898.

[3]AzevedoAS, FollainG, PatthabhiramanS, et al., 2015. Metastasis of circulating tumor cells: favorable soil or suitable biomechanics, or both? Cell Adhes Migr, 9(5):345-356.

[4]BachmannC, SchmidtS, StaeblerA, et al., 2015. CNS metastases in breast cancer patients: prognostic implications of tumor subtype. Med Oncol, 32:400.

[5]BahceciogluG, BasaraG, EllisBW, et al., 2020. Breast cancer models: engineering the tumor microenvironment. Acta Biomater, 106:1-21.

[6]Blanco-FernandezB, Rey-VinolasS, BağcıG, et al., 2022. Bioprinting decellularized breast tissue for the development of three-dimensional breast cancer models. ACS Appl Mater Interfaces, 14(26):29467-29482.

[7]BrancatoV, GioiellaF, ImparatoG, et al., 2018. 3D breast cancer microtissue reveals the role of tumor microenvironment on the transport and efficacy of free-doxorubicin in vitro. Acta Biomater, 75:200-212.

[8]The Cancer Genome Atlas Network, 2012. Comprehensive molecular portraits of human breast tumours. Nature, 490(7418):61-70.

[9]CaseyJ, YueXS, NguyenTD, et al., 2017. 3D hydrogel-based microwell arrays as a tumor microenvironment model to study breast cancer growth. Biomed Mater, 12(2):025009.

[10]CastiauxAD, SpenceDM, MartinRS, 2019. Review of 3D cell culture with analysis in microfluidic systems. Anal Methods, 11(33):4220-4232.

[11]CavalieriE, ChakravartiD, GuttenplanJ, et al., 2006. Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention. Biochim Biophys Acta Rev Cancer, 1766(1):63-78.

[12]ChafferCL, WeinbergRA, 2011. A perspective on cancer cell metastasis. Science, 331(6024):1559-1564.

[13]ChambersAF, GroomAC, MacdonaldIC, 2002. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer, 2(8):563-572.

[14]ChenK, PanH, YanZF, et al., 2021. A novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers for postoperative rapid hemostasis and prevention of tumor recurrence. Int J Biol Macromol, 182:1339-1350.

[15]ChenWJ, HoffmannAD, LiuHP, et al., 2018. Organotropism: new insights into molecular mechanisms of breast cancer metastasis. npj Precis Oncol, 2:4.

[16]ChenZZ, HanS, SannyA, et al., 2022. 3D hanging spheroid plate for high-throughput CAR T cell cytotoxicity assay. J Nanobiotechnol, 20:30.

[17]ChengF, CaoX, LiHB, et al., 2019. Generation of cost-effective paper-based tissue models through matrix-assisted sacrificial 3D printing. Nano Lett, 19(6):3603-3611.

[18]ClearyAS, LeonardTL, GestlSA, et al., 2014. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers. Nature, 508(7494):113-117.

[19]de PieriA, ByerleyAM, MusumeciCR, et al., 2020. Electrospinning and 3D bioprinting for intervertebral disc tissue engineering. JOR Spine, 3(4):e1117.

[20]DeS, JoshiA, TripathiDM, et al., 2021. Alginate based 3D micro-scaffolds mimicking tumor architecture as in vitro cell culture platform. Mater Sci Eng C, 128:112344.

[21]DhimanN, ShagaghiN, BhaveM, et al., 2021. Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model. Cytotherapy, 23(1):25-36.

[22]EckhardtBL, FrancisPA, ParkerBS, et al., 2012. Strategies for the discovery and development of therapies for metastatic breast cancer. Nat Rev Drug Discov, 11(6):479-497.

[23]ErtekinÖ, MonavariM, KrügerR, et al., 2022. 3D hydrogel-based microcapsules as an in vitro model to study tumorigenicity, cell migration and drug resistance. Acta Biomater, 142:208-220.

[24]FangJY, TanSJ, YangZ, et al., 2014. Tumor bioengineering using a transglutaminase crosslinked hydrogel. PLoS ONE, 9(8):e105616.

[25]FerreiraLP, GasparVM, MendesL, et al., 2021. Organotypic 3D decellularized matrix tumor spheroids for high-throughput drug screening. Biomaterials, 275:120983.

[26]Flores-TorresS, Peza-ChavezO, KuasneH, et al., 2021. Alginate‒gelatin‒Matrigel hydrogels enable the development and multigenerational passaging of patient-derived 3D bioprinted cancer spheroid models. Biofabrication, 13(2):025001.

[27]FongELS, HarringtonDA, Farach-CarsonMC, et al., 2016. Heralding a new paradigm in 3D tumor modeling. Biomaterials, 108:197-213.

[28]GioiellaF, UrciuoloF, ImparatoG, et al., 2016. An engineered breast cancer model on a chip to replicate ECM‐activation in vitro during tumor progression. Adv Healthcare Mater, 5(23):3074-3084.

[29]GoffSL, DanforthDN, 2021. The role of immune cells in breast tissue and immunotherapy for the treatment of breast cancer. Clin Breast Cancer, 21(1):e63-e73.

[30]GuptaGP, MassaguéJ, 2006. Cancer metastasis: building a framework. Cell, 127(4):679-695.

[31]HartlRF, 1995. Production smoothing under environmental constraints. Prod Oper Manag, 4(1):46-56.

[32]HessKR, VaradhacharyGR, TaylorSH, et al., 2006. Metastatic patterns in adenocarcinoma. Cancer, 106(7):1624-1633.

[33]HongS, SongJM, 2022. 3D bioprinted drug-resistant breast cancer spheroids for quantitative in situ evaluation of drug resistance. Acta Biomater, 138:228-239.

[34]HuangBW, GaoJQ, 2018. Application of 3D cultured multicellular spheroid tumor models in tumor-targeted drug delivery system research. J Control Release, 270:‍246-259.

[35]HutmacherDW, 2010. Biomaterials offer cancer research the third dimension. Nat Mater, 9(2):90-93.

[36]JiangT, Munguia-LopezJG, Flores-TorresS, et al., 2017. Directing the self-assembly of tumour spheroids by bioprinting cellular heterogeneous models within alginate/gelatin hydrogels. Sci Rep, 7:4575.

[37]JiangT, Munguia-LopezJG, GuK, et al., 2020. Engineering bioprintable alginate/gelatin composite hydrogels with tunable mechanical and cell adhesive properties to modulate tumor spheroid growth kinetics. Biofabrication, 12(1):015024.

[38]LangR, SternMM, SmithL, et al., 2011. Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix. Biomaterials, 32(29):7042-7052.

[39]LanzHL, SalehA, KramerB, et al., 2017. Therapy response testing of breast cancer in a 3D high-throughput perfused microfluidic platform. BMC Cancer, 17:709.

[40]LeeD, ChaC, 2020. Cell subtype-dependent formation of breast tumor spheroids and their variable responses to chemotherapeutics within microfluidics-generated 3D microgels with tunable mechanics. Mater Sci Eng C, 112:110932.

[41]LeiSY, ZhengRS, ZhangSW, et al., 2021. Global patterns of breast cancer incidence and mortality: a population-based cancer registry data analysis from 2000 to 2020. Cancer Commun, 41(11):1183-1194.

[42]LiWF, HuXY, WangSP, et al., 2019. Multiple comparisons of three different sources of biomaterials in the application of tumor tissue engineering in vitro and in vivo. Int J Biol Macromol, 130:166-176.

[43]LiXR, DengQF, ZhuangTT, et al., 2020. 3D bioprinted breast tumor model for structure‒activity relationship study. Bio Des Manuf, 3(4):361-372.

[44]LiuC, MejiaDL, ChiangB, et al., 2018. Hybrid collagen alginate hydrogel as a platform for 3D tumor spheroid invasion. Acta Biomater, 75:213-225.

[45]LiuQ, MuralidharanA, SaatehA, et al., 2022. A programmable multifunctional 3D cancer cell invasion micro platform. Small, 18(20):2107757.

[46]LuoZY, ZhangSQ, PanJJ, et al., 2018. Time-responsive osteogenic niche of stem cells: a sequentially triggered, dual-peptide loaded, alginate hybrid system for promoting cell activity and osteo-differentiation. Biomaterials, 163:25-42.

[47]LvKN, ZhuJJ, ZhengSS, et al., 2021. Evaluation of inhibitory effects of geniposide on a tumor model of human breast cancer based on 3D printed Cs/Gel hybrid scaffold. Mater Sci Eng C, 119:111509.

[48]LvYG, WangHJ, LiG, et al., 2021. Three-dimensional decellularized tumor extracellular matrices with different stiffness as bioengineered tumor scaffolds. Bioact Mater, 6(9):2767-2782.

[49]MaoSS, PangY, LiuTK, et al., 2020. Bioprinting of in vitro tumor models for personalized cancer treatment: a review. Biofabrication, 12(4):042001.

[50]MurphySV, AtalaA, 2014. 3D bioprinting of tissues and organs. Nat Biotechnol, 32(8):773-785.

[51]NathS, DeviGR, 2016. Three-dimensional culture systems in cancer research: focus on tumor spheroid model. Pharmacol Ther, 163:94-108.

[52]NothdurfterD, PlonerC, Coraça-HuberDC, et al., 2022. 3D bioprinted, vascularized neuroblastoma tumor environment in fluidic chip devices for precision medicine drug testing. Biofabrication, 14(3):035002.

[53]PeelaN, SamFS, ChristensonW, et al., 2016. A three dimensional micropatterned tumor model for breast cancer cell migration studies. Biomaterials, 81:72-83.

[54]PirasCC, SmithDK, 2020. Multicomponent polysaccharide alginate-based bioinks. J Mater Chem B, 8(36):8171-8188.

[55]PolyakK, 2007. Breast cancer: origins and evolution. J Clin Invest, 117(11):3155-3163.

[56]RedmondJ, McCarthyHO, BuchananP, et al., 2022. Development and characterisation of 3D collagen-gelatin based scaffolds for breast cancer research. Biomater Adv, 142:213157.

[57]SantoVE, EstradaMF, RebeloSP, et al., 2016. Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models. J Biotechnol, 221:118-129.

[58]SantschiM, VernengoA, EglinD, et al., 2019. Decellularized matrix as a building block in bioprinting and electrospinning. Curr Opin Biomed Eng, 10:116-122.

[59]SgroiDC, 2010. Preinvasive breast cancer. Annu Rev Pathol, 5:193-221.

[60]ShahL, LatifA, WilliamsKJ, et al., 2022. Role of stiffness and physico-chemical properties of tumour microenvironment on breast cancer cell stemness. Acta Biomater, 152:273-289.

[61]ShiXL, ChengYX, WangJ, et al., 2020. 3D printed intelligent scaffold prevents recurrence and distal metastasis of breast cancer. Theranostics, 10(23):10652-10664.

[62]StinglJ, RaoufA, EirewP, et al., 2006. Deciphering the mammary epithelial cell hierarchy. Cell Cycle, 5(14):1519-1522.

[63]SuJ, SatchellSC, WertheimJA, et al., 2019. Poly(ethylene glycol)-crosslinked gelatin hydrogel substrates with conjugated bioactive peptides influence endothelial cell behavior. Biomaterials, 201:99-112.

[64]SunYS, ZhaoZ, YangZN, et al., 2017. Risk factors and preventions of breast cancer. Int J Biol Sci, 13(11):1387-1397.

[65]SungH, FerlayJ, SiegelRL, et al., 2021. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 71(3):209-249.

[66]Tamayo-AngorrillaM, López de AndrésJ, JiménezG, et al., 2022. The biomimetic extracellular matrix: a therapeutic tool for breast cancer research. Transl Res, 247:117-136.

[67]TangYD, HuangBX, DongYQ, et al., 2017. Three-dimensional prostate tumor model based on a hyaluronic acid-alginate hydrogel for evaluation of anti-cancer drug efficacy. J Biomater Sci Polym Ed, 28(14):1603-1616.

[68]TohYC, RajaA, YuH, et al., 2018. A 3D microfluidic model to recapitulate cancer cell migration and invasion. Bioengineering, 5(2):29.

[69]TuanRS, BolandG, TuliR, 2002. Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther, 5:32.

[70]WeilbaecherKN, GuiseTA, McCauleyLK, 2011. Cancer to bone: a fatal attraction. Nat Rev Cancer, 11(6):411-425.

[71]WhitesidesGM, 2006. The origins and the future of microfluidics. Nature, 442(7101):368-373.

[72]XieMJ, GaoQ, FuJZ, et al., 2020. Bioprinting of novel 3D tumor array chip for drug screening. Bio Des Manuf, 3(3):175-188.

[73]XinX, YangH, ZhangFL, et al., 2019. 3D cell coculture tumor model: a promising approach for future cancer drug discovery. Process Biochem, 78:148-160.

[74]XuJ, FangH, ZhengSS, et al., 2021. A biological functional hybrid scaffold based on decellularized extracellular matrix/gelatin/chitosan with high biocompatibility and antibacterial activity for skin tissue engineering. Int J Biol Macromol, 187:840-849.

[75]XuX, Farach-CarsonMC, JiaXQ, 2014. Three-dimensional in vitro tumor models for cancer research and drug evaluation. Biotechnol Adv, 32(7):1256-1268.

[76]YangSJ, ZhengL, ChenZL, et al., 2022. Decellularized pig kidney with a micro-nano secondary structure contributes to tumor progression in 3D tumor model. Materials, 15(5):1935.

[77]YatesLR, KnappskogS, WedgeD, et al., 2017. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell, 32(2):169-184.e7.

[78]YueXS, NguyenTD, ZellmerV, et al., 2018. Stromal cell-laden 3D hydrogel microwell arrays as tumor microenvironment model for studying stiffness dependent stromal cell-cancer interactions. Biomaterials, 170:37-48.

[79]ZhangCR, QiuXQ, DaiY, et al., 2023. The prospects for bioprinting tumor models: recent advances in their applications. Bio-Des Manuf, 6(6):661-675.

[80]ZhangCY, YangZT, DongDL, et al., 2020. 3D culture technologies of cancer stem cells: promising ex vivo tumor models. J Tissue Eng, 11:204173142093340.

[81]ZhangQF, WangXC, KuangGZ, et al., 2022. Photopolymerized 3D printing scaffolds with Pt(IV) prodrug initiator for postsurgical tumor treatment. Research, 2022:9784510.

[82]ZhuJJ, ZhengSS, LiuHB, et al., 2021. Evaluation of anti-tumor effects of crocin on a novel 3D tissue-engineered tumor model based on sodium alginate/gelatin microbead. Int J Biol Macromol, 174:339-351.