@article {20079, title = {Enzymatically-Crosslinked Silk Fibroin Hydrogels as Artificial Matrices for the Development of a Breast Cancer 3D in vitro Model}, journal = {TERMSTEM 2019}, year = {2019}, month = {2019-11-07 00:00:00}, address = {Hotel Vila Gal{\'e} Collection, Braga, Portugal}, abstract = {

Breast cancer is one of the most common type of tumour found in women. The response to therapy varies on the genetic background of the different tumor subtypes, but in a consistent number of cases patients develop resistance to standard treatments (1). Recently, there has been an increased interest in the development of in vitro tumour models, which are used to unveil novel therapeutic strategies for anti-cancer formation and development (2, 3). The proposed work aims to generate a breast cancer 3D in vitro model, based on horseradish peroxidase (HRP)-crosslinked silk fibroin (SF) hydrogel matrices. MCF7 breast cancer cells and human mammary fibroblasts (HMF) were encapsulated into SF hydrogels, and their viability was tested at different time points. From the preliminary obtained results, MCF7 cells co-cultured with HMF showed an increased proliferation and spheroid-like aggregates formation already in the first days of testing, as compared to MCF7 monoculture. In addition, cells in co-culture exhibited an upregulation of the expression of genes related to the extracellular matrix remodelling (collagens, MMPs) and to the activation of normal fibroblasts into cancer associated ones (α-SMA, vimentin). The potentiality to trigger angiogenic mechanisms will be further assayed by means of using the chorioallantoic membrane (CAM) assay. Overall, our results suggest that SF hydrogels are adequate matrices for the development of a heterotypic breast cancer in vitro model, to be further exploited to unravel novel molecular targets for therapy.

Acknowledgments: This work is supported by the projects FROnTHERA-RL1 (Ref. NORTE-01-0145-FEDER-000023), BREAST-IT (PTDC/BTM-ORG/28168/2017), Fun4TE (PTDC/EMD-EMD/31367/2017) and by EU Framework Programme for Research and Innovation H2020 on FoReCaST (Forefront Research in 3D Disease Cancer Models as in vitro Screening Technologies) under grant agreement no.668983. The FCT distinctions attributed to J.M. Oliveira (IF/01285/2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.

References

1) Waks, A. G. \& Winer, E. P. JAMA - J. Am. Med. Assoc. 321, 288{\textendash}300 (2019).

2) Rodrigues, T. et al. Pharmacol Ther 184, 201{\textendash}211 (2018).

3) Carvalho, MR et al. Stem Cell Rev Rep, Jun 13(3), 347{\textendash}363 (2017).

}, keywords = {3D tumor model, breast cancer, Drug testing, Silk Fibroin}, author = {Pierantoni, L. and Brancato, V. and Silva-Correia, J. and Kundu, S. C. and Reis, R. L. and Oliveira, J. M.} }