We are delighted to announce that a very interesting study using BIOMIMESYS® to study the metastasis of breast cancer has been published in Experimental Hematology & Oncology Journal (Impact factor 11,4).

This article untitled “ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells” (Cicero, Trouvilliez, et al. 2023) highlights the importance of the Extracellular Matrix organ specificity in breast cancer metastasis behavior. In this context, BIOMIMESYS® Brain and BIOMIMESYS® Liver matrices, which differ in both composition and stiffness to fully reproduce the organ microenvironment, has made possible to reproduce in vitro brain and liver metastasis behavior similar to that observed on mice. These results demonstrated that BIOMIMESYS® represents a powerful tool to study in vitro metastasis propagation, as well as an interesting alternative to animal testing.

Fig. 5 extract: TrkA/EphA2 increases TNBC persistence in brain‑like ECM. Representative confocal images of TrkA/EphA2 PLA and phosphorylated Src (active form) signal inside MDA‑MB‑231‑TrkA‑KD incubated in brain‑like or liver‑like ECM. Source: https://ehoonline.biomedcentral.com/articles/10.1186/s40164-023-00463-6

We are very pleased to closely collaborate with Robert-Alain Toillon’s teams UMR9020-U1277 – CANTHER – Cancer Heterogeneity Plasticity and Resistance to Therapies (ONCOLille, lead by Dr. Isabelle Van Seuningen). Thanks to Julien Cicero for carrying out the experiment using BIOMIMESYS® as a part of his PhD project, and congratulation to all authors for their amazing work!


Background: Triple-Negative Breast Cancer is particularly aggressive, and its metastasis to the brain has a significant psychological impact on patients’ quality of life, in addition to reducing survival. The development of brain metastases is particularly harmful in triple-negative breast cancer (TNBC). To date, the mechanisms that induce brain metastasis in TNBC are poorly understood.

Methods: Using a human blood-brain barrier (BBB) in vitro model, an in vitro 3D organotypic extracellular matrix, an ex vivo mouse brain slices co-culture and in an in vivo xenograft experiment, key step of brain metastasis were recapitulated to study TNBC behaviors.

Results: In this study, we demonstrated for the first time the involvement of the precursor of Nerve Growth Factor (proNGF) in the development of brain metastasis. More importantly, our results showed that proNGF acts through TrkA independent of its phosphorylation to induce brain metastasis in TNBC. In addition, we found that proNGF induces BBB transmigration through the TrkA/EphA2 signaling complex. More importantly, our results showed that combinatorial inhibition of TrkA and EphA2 decreased TBNC brain metastasis in a preclinical model.

Conclusions: These disruptive findings provide new insights into the mechanisms underlying brain metastasis with proNGF as a driver of brain metastasis of TNBC and identify TrkA/EphA2 complex as a potential therapeutic target.

(Full text here)


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