腫瘍モデルの改良でがん治療法の探索を最適化(Upgraded tumor model optimizes search for cancer therapies)

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2023-03-20 ライス大学

米国のライス大学の研究者たちは、骨肉腫細胞とマクロファージと呼ばれる免疫細胞を3次元構造に収め、がん細胞が化学療法に対してどのように反応するかを調べるアップグレードされた腫瘍モデルを開発した。
この研究により、免疫反応ががん細胞の抵抗性を高めることがわかった。従来の腫瘍モデルにはない、免疫細胞など環境因子を考慮したモデルの開発は、より効果的ながん治療法の開発につながる可能性がある。また、個人の腫瘍の特徴を用いた治療モデルの開発も視野に入れている。

<関連情報>

骨肉腫の力学的に調整可能な人工モデルにおいて、腫瘍関連マクロファージが炎症と薬剤耐性を誘導することがわかった Tumor-associated macrophages induce inflammation and drug resistance in a mechanically tunable engineered model of osteosarcoma

Letitia K. Chim, Isabelle L. Williams, Caleb J. Bashor, Antonios G. Mikos
Biomaterials  Available online: 7 March 2023
DOI:https://doi.org/10.1016/j.biomaterials.2023.122076

腫瘍モデルの改良でがん治療法の探索を最適化(Upgraded tumor model optimizes search for cancer therapies)

Abstract

The tumor microenvironment is a complex and dynamic ecosystem composed of various physical cues and biochemical signals that facilitate cancer progression, and tumor-associated macrophages are especially of interest as a treatable target due to their diverse pro-tumorigenic functions. Engineered three-dimensional models of tumors more effectively mimic the tumor microenvironment than monolayer cultures and can serve as a platform for investigating specific aspects of tumor biology within a controlled setting. To study the combinatorial effects of tumor-associated macrophages and microenvironment mechanical properties on osteosarcoma, we co-cultured human osteosarcoma cells with macrophages within biomaterials-based bone tumor niches with tunable stiffness. In the first 24 h of direct interaction between the two cell types, macrophages induced an inflammatory environment consisting of high concentrations of tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 within moderately stiff scaffolds. Expression of Yes-associated protein (YAP), but not its homolog, transcriptional activator with PDZ-binding motif (TAZ), in osteosarcoma cells was significantly higher than in macrophages, and co-culture of the two cells slightly upregulated YAP in both cells, although not to a significant degree. Resistance to doxorubicin treatment in osteosarcoma cells was correlated with inflammation in the microenvironment, and signal transducer and activator of transcription 3 (STAT3) inhibition diminished the inflammation-related differences in drug resistance but ultimately did not improve the efficacy of doxorubicin. This work highlights that the biochemical cues conferred by tumor-associated macrophages in osteosarcoma are highly variable, and signals derived from the immune system should be considered in the development and testing of novel drugs for cancer.

医療・健康
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