Tumor-Stroma Interactions Alter the Sensitivity of Drug in Breast Cancer

Abstract

Flat cell cultures or xenografts are inadequate tools to unravel cancer complex biology. 3D in vitro tumor models garnered interest since they recapitulate better dynamic mechanisms of cancer, but a gold standard model that faithfully mimics solid cancer is not available yet. 3D breast cancer model is fabricated using freeze-dried silk fibroin scaffolds. Breast cancer cell lines (MCF-7 and MDA-MB231) are seeded with normal mammary fibroblasts onto silk fibroin scaffold (1 and 2 mm thick). Cells proliferation is monitored by means of Alamar blue assay. 3D breast cancer models morphology is observed by confocal microscopy. Gene expression modulation concerning extracellular matrix markers is evaluated. Further, 3D bioengineered breast cancer models are treated with doxorubicin. Silk fibroin scaffolds allow the proliferation of cancer cells and fibroblasts. Cells growth is enhanced when cancer cells and fibroblasts are seeded together. Histological staining shows 3D cell organization. MMP-1, MMP-2, MMP-3, Col-1, and Fibronectin expression is upregulated in co-culture. After doxorubicin treatment, stronger reduction in cell activity is observed in 2 mm SF scaffold in comparison to 1 mm. The 3D in vitro breast cancer model obtained can easily be scaled-up and translated to the preclinical testing of novel chemotherapeutics.

Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology

“…These cellular models are small formations that closely mimic the natural tumor microenvironment without the complexity and cost of maintaining animal colonies needed for in vivo studies (Brancato et al, 2017(Brancato et al, , 2018. As sensitivity of cancer cells to drug treatment is strongly influenced by the tumor stroma (Brancato et al, 2020;Landry et al, 2018), the 3D microtissues developed from our PDX lines are an ideal platform to study drug response of MPNST. The collagen matrix used in our 3D microtissues, which is absent in traditional 2D culture, favors cellcell interactions by mimicking the ECM (Brett et al, 2016;Crampton et al, 2018).…”

Homemade Bread: Repurposing an Ancient Technology forin vitroTissue Engineering

“…To assess the viability and metabolic activity of the cells at Day 1 and Day 13 after seeding, we employed the alamar blue assay, which has been successfully used on 3D scaffolds [25] (Fig. 5a).…”

“…By Day 13 cell density on the BB and xBB scaffolds is the same at 2308 ± 339 cells/mm 2 vs 1968 ± 494 cells/mm 2 , respectively (p = 0.94569). We also assessed the viability and metabolic activity of the cells at Day 1 and Day 13 with an alamar blue assay, which has been successfully used on 3D scaffolds [28] (Supplementary Fig. 2).…”

Recapitulation of dynamic nanoparticle transport around tumors using a triangular multi-chamber tumor-on-a-chip

“…23,24 In addition, the ECM can not only regulate the growth of cells but also affect the phenotypic changes, drug uptake and drug sensitivity of tumor cells. 25…”

“…23,24 In addition, the ECM can not only regulate the growth of cells but also affect the phenotypic changes, drug uptake and drug sensitivity of tumor cells. 25 In this study, the formulations of GelMA/gelatin composite bioinks were systematically optimized to meet the requirements of perfusion on the chip and long-term support of the 3D growth of tumor cells. In addition, some biological features of 3D tumor tissues including epithelial transformation (EMT), hypoxia and proliferation activities were studied in the TM-CTC platform.…”