Arciero Ilaria, Buonvino Silvia, Palumbo Valeria, Scimeca Manuel, Melino Sonia
Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", Via Della Ricerca Scientifica 1, 00133 Rome, Italy.
Departmental Faculty of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant'Alessandro 8, 00131 Rome, Italy.
Int J Mol Sci. 2024 Dec 5;25(23):13068. doi: 10.3390/ijms252313068.
Breast cancer is the most common cancer and the second leading cause of cancer-related death in women. In advanced stages of the disease, breast cancer can spread and metastasize to the bone, contributing to malignant progression. The roles of tissue stiffness and remodeling of the tumor microenvironment are relevant in influencing cancer progression and invasiveness, but they are still poorly understood. In this study, we aimed to investigate the effect of bone tissue stiffness on breast cancer cell behavior, using 3D cell-biomaterial systems to model the in vivo conditions. For this purpose, we developed a 3D-printable cell array, which is a tunable and reproducible platform on small scale, where each compartment could mimic the physiological cancer environment with a shape and rigidity close to bone tissue. In this system, we observed that in the highly metastatic breast cancer line MDA-MB-231, embedded in PEG-silk fibroin (PSF) hydrogel spheres in the array's cavities, increasing stiffness promotes trans-differentiation into osteoblast-like cells and the production of breast microcalcifications. Moreover, we also tested this 3D model as a platform to evaluate the cell response to the therapy, in particular, investigating the drug sensitivity of the cancer cells to chemotherapeutics, observing a decrease in drug resistance over time in the array.
乳腺癌是女性中最常见的癌症，也是癌症相关死亡的第二大主要原因。在疾病的晚期，乳腺癌会扩散并转移至骨骼，导致恶性进展。组织硬度和肿瘤微环境重塑在影响癌症进展和侵袭性方面发挥着作用，但目前仍知之甚少。在本研究中，我们旨在利用三维细胞-生物材料系统模拟体内条件，研究骨组织硬度对乳腺癌细胞行为的影响。为此，我们开发了一种可3D打印的细胞阵列，这是一个小规模的可调谐且可重复的平台，其中每个隔室都可以模拟生理癌症环境，其形状和硬度接近骨组织。在这个系统中，我们观察到，在高度转移性乳腺癌细胞系MDA-MB-231中，当嵌入阵列腔中的聚乙二醇-丝素蛋白（PSF）水凝胶球时，硬度增加会促进其向成骨样细胞转分化并产生乳腺微钙化。此外，我们还将这个三维模型作为一个平台来评估细胞对治疗的反应，特别是研究癌细胞对化疗药物的敏感性，观察到阵列中癌细胞的耐药性随时间下降。
