Dataset Information

Cancer-associated fibroblasts shape microenvironment dynamics in a 3D bioprinted breast cancer model

ABSTRACT: Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment. Here, we show that microextrusion bioprinting can reproducibly produce distinct cancer and stromal compartments integrating cells relevant to human pathology. Our findings unveil the functional maturation of this millimeter-sized model, showcasing the development of a hypoxic cancer core and an increased surface proliferation. Maturation was also driven by the presence of cancer-associated fibroblasts (CAF) that induced elevated microvascular-like structures complexity. Such modulation was concomitant to extracellular matrix remodeling, with high levels of collagen and matricellular proteins deposition by CAF, simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development. Importantly, our bioprinted model faithfully reproduced response to treatment, further modulated by CAF. Notably, CAF played a protective role for cancer cells against radiotherapy, facilitating increased paracrine communications. This model holds promise as a platform to evaluate microenvironment targeting drugs in a human pathology relevant context, that could lead to significant improvements for patient care.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Bos Taurus (bovine)

DISEASE(S): Breast Cancer

SUBMITTER: Dupuy Jean-William

LAB HEAD: Hugo De Oliveira

PROVIDER: PXD050584 | Pride | 2024-12-17

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Link_between_files.xlsx	Xlsx
	RP_UP000005640_Homo_sapiens_2023_09_13.fasta	Fasta
	RP_UP000009136_Bos_taurus_2023_11_09.fasta	Fasta
	checksum.txt	Txt
	jcf221215_01.msf	Msf

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Publications

3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity.

Desigaux Theo T Comperat Leo L Dusserre Nathalie N Stachowicz Marie-Laure ML Lea Malou M Dupuy Jean-William JW Vial Anthony A Molinari Michael M Fricain Jean-Christophe JC Paris François F Oliveira Hugo H

Bioactive materials 20240905

Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment. Here, we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology. Our findings unveil the functional maturation of this millimeter-sized model, showcasing the development of a hypoxic cancer core and an increased surface prolifer ...[more]

PMID: 39290339

Similar Datasets

Project description:To study of differential effect on cancer-associated fibroblasts of HNSCC, we have employed microarray expression profiling. The critical effect of the tumor microenvironment to caner progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may attributed to fibroblasts. However, little is known about fibroblasts that inhibit cancer progression. From the immunohistochemical analysis of cancer tissues from head and neck squamous cell carcinoma (HNSCC) patients, we divided cancer-associated fibroblast (CAF) into two groups depending on whether the boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM) is clear and smooth or not. Therefore, we tried to evaluate whether there is a difference between these two CAFs in HNSCC progression. CAF was primary cultured, followed by co-culture with HNSCC cell to observe the effect on Matrigel invasion. The mRNA expression patterns between these two CAF groups were compared by DNA microarray analysis. FaDu cell and primary CAF from each group was co-transplanted into the oral mucosa of mice, and the tumorigenesis was compared. The CAF group (CAF-Promote, CAF-P) from cancer tissues which have unclear boundary between ECM and epithelial cancer cells showed a tendency to stimulate in vitro Matrigel invasion of HNSCC cell. On the contrary, the CAF group (CAF-Defense, CAF-D) from cancer tissues, which have clear boundary with epithelial cancer cell caused no remarkable increase of Matrigel invasion. In addition, CAF-D reduced the tumorigenicity of FaDu compared to CAF-P in the in vivo mice model. In DNA microarray analysis, COL3A1, COL6A6, COL25A1, and COL26A1 were particularly highly expressed in CAF-D group. In this study, these collagen proteins derived from cancer stroma were found to have a function of inhibiting the progression of HNSCC. It is expected to provide important information for predicting the prognosis of HNSCC and development of drug target in the future.