PXD067876-1

PXD067876 is an original dataset announced via ProteomeXchange.

Title	A Vascularized Three-Dimensional Breast Cancer Model: Mimicking the Tumor Microenvironment and Chemoresistance
Description	Tumorigenesis is a complex and dynamic process in which the tumor microenvironment (TME) plays a central role. In solid tumors, the TME contributes to key mechanisms of tumor progression, including metastasis, immune evasion, and resistance to therapies. One major challenge in preclinical cancer research is the development of reliable three-dimensional (3D) in vitro models, which more accurately replicate the in vivo tumor architecture and microenvironmental conditions, such as hypoxia and extracellular matrix (ECM) organization. However, reproducing functional vascular networks and neo-angiogenesis within these models remains a key challenge. In this study, an advanced 3D tumor model, referred to as angiotumoroids, was developed by co-culturing primary murine breast tumor cells (PTCs) with species-specific adipose-derived microvascular fragments (MVFs). Angiotumoroids successfully integrated MVFs, resulting in the formation of vasculature-like structures and demonstrated robust structural organization with a dynamic modulation of matrix metalloproteinase 9 (MMP9). Formation of neovasculature was visualized through sprouting and branching, driven by both direct PTC–MVF interactions and PTC-conditioned media, underscoring the importance of juxtacrine and paracrine signaling in vascular development within the tumor model. To further characterize these structures, high-resolution proteomic profiling was performed, revealing distinct patterns associated with angiogenesis, ECM composition, and remodeling. Angiotumoroids exhibited a unique proteomic signature, including differential expression of several angiogenic factors. ECM analysis confirmed the presence of collagen types I and IV and elevated expression of MMPs, highlighting active ECM remodeling. Additionally, the proteomic data revealed increased levels of ATP-binding cassette (ABC) transporters, particularly ABCB1 (P-glycoprotein), potential mechanisms of drug efflux. Functionally, angiotumoroids exhibited reduced sensitivity to doxorubicin compared to PTC spheroids, maintaining structural integrity and higher cell viability post-treatment. Time-course analysis of doxorubicin uptake revealed preferential accumulation in MVF-enriched regions, as confirmed by colocalization with CD31, pointing to a spatially regulated drug distribution pattern mediated by the vascular compartment. Collectively, these findings establish angiotumoroids as a robust and physiologically relevant in vitro model for investigating tumor vascularization, ECM dynamics, and therapeutic response. This platform holds significant promise for predictive cancer research and preclinical drug screening, bridging the gap between traditional in vitro systems and in vivo models
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-22_16:42:38.436.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Margot Lo Pinto
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-29 06:43:43	ID requested
⏵ 1	2026-02-22 16:42:39	announced

10.1186/s12935-025-04154-6;

Lo Cicero A, La Monica F, Lo Buglio G, Campora S, Gangemi F, Cin, à P, Salamone M, Lo Pinto M, Scilabra SD, Ghersi G, A vascularized three-dimensional model integrating primary breast tumor cells and microvascular fragments: mimicking the tumor microenvironment involved in chemoresistance. Cancer Cell Int, 26(1):74(2026) [pubmed]

submitter keyword: Angiogenesis

Spheroids

Microvascular fragments

Tumor microenvironment

3D tumor model

Simone Dario Scilabra
contact affiliation	Fondazione Ri.Med Department of Laboratory Medicine and Advanced Biotechnologies, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS - ISMETT) Via Ernesto Tricomi, 5 - 90127 Palermo
contact email	sdscilabra@fondazionerimed.com
lab head
Margot Lo Pinto
contact affiliation	Fondazione Ri.MED
contact email	mlopinto@fondazionerimed.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/02/PXD067876

PRIDE project URI

• PRIDE
  1. PXD067876
     1. Label: PRIDE project
     2. Name: A Vascularized Three-Dimensional Breast Cancer Model: Mimicking the Tumor Microenvironment and Chemoresistance