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CURATOR
A pinboard by
Aranzazu Villasante

Postdoc, Columbia University

PINBOARD SUMMARY

I am a cancer engineer and I build in vitro models of pediatric cancers

My research interest is in an emerging area of bioengineering that is cancer engineering. The overarching goal of this field is to build controllable models that can faithfully recapitulate human cancer in vitro, by establishing a transdisciplinary approach that combines tools from molecular biology, bioengineering and medicine. The rationale behind this approach is that by better mimicking clinical situations, more reliable preclinical study results will be generated and better therapies will be developed.
Based on skills and knowledge that I acquired over the years, my line of research involves strong expertise in epigenetics, cancer, stem cell biology and bioengineering. Specifically, I am interested in drug-resistance and tumor relapse. Tumor relapse is the major cause of succumbing to the disease, and properties attributed to cancer stem-like cells, such as drug-resistance and cell plasticity, seem to be the key mechanisms. However, the lack of controllable models that recapitulate human cancer features limits our understanding of the process and impedes the development of new therapies. I recently demonstrated the undesirable effect of current treatments (isotretionin) in neuroblastoma. I showed the existence of resistant sub-populations of neuroblastoma cells with different levels of stemness that could be related to the capacity to transdifferentiate into endothelial-like cells. Formation of a new and alternative vascular network, for which there is no effective therapy, could explain in part the lack of clinical benefit observed with isotretinoin in the treatment of high-risk neuroblastoma. Tissue-engineered tumor models could thus bridge the gap between current in vitro cultures and animal models towards a better understanding of neuroblastoma tumor biology and development of new therapeutic modalities.

5 ITEMS PINNED

Recapitulating the Size and Cargo of Tumor Exosomes in a Tissue-Engineered Model.

Abstract: There is a growing interest in the pivotal role of exosomes in cancer and in their use as biomarkers. However, despite the importance of the microenvironment for cancer initiation and progression, monolayer cultures of tumor cells still represent the main in vitro source of exosomes. As a result, their environmental regulation remains largely unknown. Here, we report a three-dimensional tumor model for studying exosomes, using Ewing's sarcoma type 1 as a clinically relevant example. The bioengineered model was designed based on the hypothesis that the 3-dimensionality, composition and stiffness of the tumor matrix are the critical determinants of the size and cargo of exosomes released by the cancer cells. We analyzed the effects of the tumor microenvironment on exosomes, and the effects of exosomes on the non-cancer cells from the bone niche. Exosomes from the tissue-engineered tumor had similar size distribution as those in the patients' plasma, and were markedly smaller than those in monolayer cultures. Bioengineered tumors and the patients' plasma contained high levels of the Polycomb histone methyltransferase EZH2 mRNA relatively to their monolayer counterparts. Notably, EZH2 mRNA, a potential tumor biomarker detectable in blood plasma, could be transferred to the surrounding mesenchymal stem cells. This study provides the first evidence that an in vitro culture environment can recapitulate some properties of tumor exosomes.

Pub.: 10 Jun '16, Pinned: 17 Aug '17

Tissue-engineered models of human tumors for cancer research.

Abstract: Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research.In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing.While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function.

Pub.: 11 Feb '15, Pinned: 17 Aug '17