Dataset Information

Xenografted Tumor decellularization provides cell-specific in vitro 3D environment

ABSTRACT: In vitro cell culture studies are common in cancer research field, and reliable biomimetic 3D models are needed to ensure physiological relevance. In this manuscript, we hypothesized that decellularized xenograft tumors can serve as an optimal 3D substrate to generate a top-down approach for in vitro tumor modeling. Methods: Multiple tumor cell lines were xenografted and the formed solid tumors were recovered for their decellularization by several techniques and further characterization by histology and proteomics techniques. Selected decellularized tumor xenograft samples were seeded with human triple negative breast cancer (TNBC)c ells and cell behavior was compared among them and with other control 2D and 3D cell culture methods. Results: A soft treatment using Freeze-EDTA-DNAse allows proper decellularization of xenografted tumor samples. Interestingly, proteomic data show that samples decellularized from TMBC xenograft models had different extracellular matrix (ECM) composition compared to the rest of xenograft tumors tested. The in vitro re-cellularization of decellularized ECM (dECM) yields tumor-type specific cell-behavior in TNBC context. Conclusions: Data indicate that dECM derived from xenograft tumors is a feasible substrate for re-seeding purposes, thereby promoting tumor-type specific cell behavior. These data serve as a proof-of-concept for further potential generation of patient-specific in vitro research models.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

SUBMITTER: Mikel Azkargorta

LAB HEAD: Felix Elortza

PROVIDER: PXD034597 | Pride | 2022-09-12

REPOSITORIES: Pride

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Publications

Decellularization of xenografted tumors provides cell-specific in vitro 3D environment.

Iazzolino Gaia G Mendibil Unai U Arnaiz Blanca B Ruiz-de-Angulo Ane A Azkargorta Mikel M Uribe Kepa B KB Khatami Neda N Elortza Felix F Olalde Beatriz B Gomez-Vallejo Vanessa V Llop Jordi J Abarrategi Ander A

Frontiers in oncology 20220818

In vitro cell culture studies are common in the cancer research field, and reliable biomimetic 3D models are needed to ensure physiological relevance. In this manuscript, we hypothesized that decellularized xenograft tumors can serve as an optimal 3D substrate to generate a top-down approach for in vitro tumor modeling. Multiple tumor cell lines were xenografted and the formed solid tumors were recovered for their decellularization by several techniques and further characterization ...[more]

PMID: 36059712

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Project description:Rationale: Cardiac extracellular matrix (ECM) comprises a dynamic molecular network providing structural support to heart tissue function. Understanding the impact of ECM remodeling on cardiac cells during heart failure (HF) is essential to prevent adverse ventricular remodeling and restore organ functionality in affected patients. Objectives: We aimed to (i) identify consistent modifications to cardiac ECM structure and mechanics that contribute to HF and (ii) determine the underlying molecular mechanisms. Methods and Results: We first performed decellularization of human and murine ECM (dECM) and then analyzed the pathological changes occurring in dECM during HF by atomic force (AFM), two-photon microscopy, high-resolution 3D image analysis and computational fluid dynamics (CFD) simulation. We then performed molecular and functional assays in patient-derived cardiac fibroblasts (CFs) based on YAP-TEAD mechanosensing activity and collagen contraction assays. The analysis of HF dECM resulting from ischemic (IHD) or dilated cardiomyopathy (DCM), as well as from mouse infarcted tissue, identified a common pattern of modifications in their 3D topography. As compared to healthy heart, HF ECM exhibited aligned, flat and compact fiber bundles, with reduced elasticity and organizational complexity. At the molecular level, RNA sequencing of HF CFs highlighted the overrepresentation of dysregulated genes involved in ECM organization, or being connected to TGFß1, Interleukin-1, TNF-alpha and BDNF signaling pathways. Functional tests performed on HF CFs pointed at mechanosensor YAP as a key player in ECM remodeling in the diseased heart via transcriptional activation of focal adhesion assembly. Finally, in vitro experiments clarified pathological cardiac ECM prevents cell homing, thus providing further hints to identify a possible window of action for cell therapy in cardiac diseases. Conclusions: Our multi-parametric approach has highlighted repercussions of ECM remodeling on cell homing, CF activation and focal adhesion protein expression via hyper-activated YAP signaling during HF. Key words: Decellularization, extracellular matrix, dilated cardiomyopathy, ischemic heart disease, YAP, dilated cardiomyopathy, mechanobiology.

Dataset Information

Xenografted Tumor decellularization provides cell-specific in vitro 3D environment

Publications

Decellularization of xenografted tumors provides cell-specific <i>in vitro</i> 3D environment.

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