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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 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 decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology., Competing Interests: All authors declare that there is no conflict of interest., (© 2024 The Authors.)

Immune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of ß-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic ß-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of ß-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated ß-catenin represses expression of SDC4 and RAB27A , two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated ß-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of β-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic ß-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of ß-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response., Competing Interests: CD, JV, AB, IM, AR, JD, MP, PB, DP, ND, MV, BB, CB, VM No competing interests declared, (© 2024, Dantzer et al.)

Bioprinting applications in the clinical field generate great interest, but developing suitable biomaterial inks for medical settings is a challenge. Placental tissues offer a promising solution due to their abundance, stability, and status as medical waste. They contain basement membrane components, have a clinical history, and support angiogenesis. This study formulates bioinks from two placental tissues, amnion (AM) and chorion (CHO), and compares their unique extracellular matrix (ECM) and growth factor compositions. Rheological properties of the bioinks are evaluated for bioprinting and maturation of human endothelial cells. Both AM and Cho-derived bioinks sustained human endothelial cell viability, proliferation, and maturation, promoting optimal vasculogenesis. These bioinks derived from human sources have significant potential for tissue engineering applications, particularly in supporting vasculogenesis. This research contributes to the advancement of tissue engineering and regenerative medicine, bringing everyone closer to clinically viable bioprinting solutions using placental tissues as valuable biomaterials., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Entosis is a process that leads to the formation of cell-in-cell structures commonly found in cancers. Here, we identified entosis in hepatocellular carcinoma and the loss of Rnd3 (also known as RhoE) as an efficient inducer of this mechanism. We characterized the different stages and the molecular regulators of entosis induced after Rnd3 silencing. We demonstrated that this process depends on the RhoA/ROCK pathway, but not on E-cadherin. The proteomic profiling of entotic cells allowed us to identify LAMP1 as a protein upregulated by Rnd3 silencing and implicated not only in the degradation final stage of entosis, but also in the full mechanism. Moreover, we found a positive correlation between the presence of entotic cells and the metastatic potential of tumors in human patient samples. Altogether, these data suggest the involvement of entosis in liver tumor progression and highlight a new perspective for entosis analysis in medicine research as a novel therapeutic target., (© 2024. The Author(s).)