Tumor Models

Create an Ideal Tumor Microenvironment.  Fight Cancer.

Tumor microenvironments are dynamic and complex: they are composed of multiple cell types[1], chemical gradients[2], and extracellular matrix components[3],[4].  The stiffness of the extracellular matrix also regulates tumor behavior[5],[6],[7].  Novel discoveries in cancer biology and treatment will require researchers to use tools that help create relevant and predictive models to uncover new mechanisms and therapies.

BRTI Life Sciences Cancer Research Image
BRTI Life Sciences Stem Cell Research Image

Why 2D Cultures Are Poor Models for Identifying New Cancer Therapies

2D cultures poorly represent tumor microenvironments and limit cellular mechanisms that can be targeted in drug discovery.  Cancer cells propagated in 2D:

 

  • Express less extracellular matrix proteins compared to 3D[8]
  • Only contact other cells in one plane
  • Express adhesion and migration proteins differently compared to 3D[9]
  • Exhibit higher proliferation rate compared to 2D[10]

Consequently, therapeutics that target cell-cell communication and interaction, cell-matrix interactions, adhesion, extravasation, and migration may be overlooked while therapeutics that target cell proliferation may appear artificially promising.

Research Suggests 3D Cultures Create a Better Tumor Model

 

Cell-cell interactions, extracellular matrix components, chemical gradients, growth rates, and gene expression in 3D have been shown to provide more clinical relevance compared to cells in 2D culture[11],[12].

Create Custom 3D Tumor Models with Cell-Mate3D

  • Culture cancer cells with cancer associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), and others cell types to mimic the cellular heterogeneity of tumors
  • Add cytokines, growth factors and pharmaceuticals to culture media to study migration, extravasation, and epithelial to mesenchymal transition (EMT).
  • Replace up to 10% of hydration fluid with other basement membrane proteins for further customization

Cell-Mate3DTM Has Advantages Over Other 3D Options Because It:

  • Exhibits tissue-like stiffness, mimicking the natural cell environment
  • Permits long-term 3D cultures without producing a necrotic core
  • Allows for chemical gradients, which could increase tumor complexity
  • Binds CD44 cell adhesion protein, allowing for cell-matrix interaction

Researchers benefit because Cell-Mate3D is:

  • Chemically defined
  • Injectable for use in animal models
  • NO chemical or UV crosslinking required
  • Efficient and easy to use
References

[1] Paolo Cirri, Paola Chiarugi. Cancer associated fibroblasts: the dark side of the coin. Am J Cancer Res 2011.1(4):482-497

[2] Brendon M. Baker et al. Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues. J Cell Sci 2012.  125 (Pt 13):3015-3024

[3] Soo-Hyun Kim et al. Extracellular matrix and cell signaling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol 2011. 209(2):139-151

[4] Tijana Borovski et al. Cancer Stem Cell Niche: The Place to Be. Cancer Res 2011. 71(3):634-639

[5] Robert W. Tilghman et al. Matrix Rigidity Regulates Cancer Cell Growth by Modulating Cellular Metabolism and Protein Synthesis. PLoS One 2012.7(5):e37231

[6] V. Seewaldt. ECM stiffness paves the way for tumor cells. Nat Med 2014. 20(4): 332–333

[7] J. K. Mouw, et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat Med 2014. 20(4):360–367

[8] Oliver Zschenker et al. Genome-Wide Gene Expression Analysis in Cancer Cells Reveals 3D Growth to Affect ECM and Processes Associated with Cell Adhesion but Not DNA Repair. PLoS One 2012 7(4): e34279

[9] Oliver Zschenker et al. Genome-Wide Gene Expression Analysis in Cancer Cells Reveals 3D Growth to Affect ECM and Processes Associated with Cell Adhesion but Not DNA Repair. PLoS One 2012 7(4): e34279

[10] Anna C. Luca et al. Impact of the 3D Microenvironment on Phenotype, Gene Expression, and EGFR Inhibition of Colorectal Cancer Cell Lines. PLoS One 2013. 8(3): e59689

[11] Kenny Chitcholtan et al. The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer.  J Transl Med 2012. 10(38)

[12] Modeling genetic and clinical heterogeneity in epithelial ovarian cancers. Carcinogenesis 2011. 32(10) 1540–1549

Analyze your Cell-Mate3D™ cultures using common laboratory techniques