Three-dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer

Cancer Medicine
Natalie FalkenbergNatasa Anastasov

Abstract

A 3D microtissues using T47D and JIMT-1 cells were generated to analyze tissue-like response of breast cancer cells after combined human epidermal growth factor receptor 2 (HER2)-targeted treatment and radiation. Following lentiviral knockdown of HER2, we compared growth rate alterations using 2D monolayers, 3D microtissues, and mouse xenografts. Additionally, to model combined therapeutic strategies, we treated HER2-depleted T47D cells and 3D microtissues using trastuzumab (anti-HER2 antibody) in combination with irradiation. Comparison of HER2 knockdown with corresponding controls revealed growth impairment due to HER2 knockdown in T47D 2D monolayers, 3D microtissues, and xenografts (after 2, 12, and ≥40 days, respectively). In contrast, HER2 knockdown was less effective in inhibiting growth of trastuzumab-resistant JIMT-1 cells in vitro and in vivo. Combined administration of trastuzumab and radiation treatment was also analyzed using T47D 3D microtissues. Administration of both, radiation (5 Gy) and trastuzumab, significantly enhanced the growth inhibiting effect in 3D microtissues. To improve the predictive power of potential drugs--as single agents or in combination--here, we show that regarding tumor growth analyses, 3D ...Continue Reading

References

Apr 9, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M WartenbergH Sauer
Aug 22, 2003·Nature·Alison Abbott
Mar 28, 2008·Cancer Chemotherapy and Pharmacology·Matthew E HardeeMark W Dewhirst
Jun 24, 2010·Current Opinion in Pharmacology·Ian A CreeAlan L Harvey
Aug 14, 2012·The Journal of Gene Medicine·Ines HöfigNataša Anastasov
Oct 24, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nadire DuruJian Jian Li
Dec 12, 2012·Radiation Oncology·Nataša AnastasovMichael J Atkinson
Jan 15, 2013·International Journal of Radiation Biology·Ioannis F VoutsasConstantin N Baxevanis
Mar 19, 2014·Advanced Drug Delivery Reviews·Claudio R ThomaWilhelm Krek

❮ Previous
Next ❯

Citations

Jul 3, 2016·Drug Discovery Today·Maria Chatzinikolaidou
Aug 9, 2016·Trends in Biotechnology·Nathalie Picollet-D'hahanDonald K Martin
Jan 10, 2017·International Journal of Radiation Biology·Vanja RadulovicNataša Anastasov
Jun 16, 2017·Lab on a Chip·Boyang Zhang, Milica Radisic
Jun 21, 2020·Drug Discovery Today·Sean LinKamyar Hadian

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
fluorescence microscopy
xenograft
biopsies
reverse transcription PCR

Software Mentioned

Harmony
Operetta
SigmaPlot

Related Concepts

Related Feeds

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.