Alberta Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P. R. China.
Joint Research Centre on Medicine, Xiangshan Hospital of Wenzhou Medical University, Ningbo, Zhejiang 315700, P. R. China.
Langmuir. 2024 Jul 16;40(28):14476-14485. doi: 10.1021/acs.langmuir.4c01227. Epub 2024 Jul 5.
Breast cancer is a common malignant tumor arising in normal mammary epithelial tissues. Nearly 75% of the patients with advanced mammary cancer develop bone metastases, resulting in secondary tumor growth, osteolytic bone degradation, and poor prognosis. The bone matrix comprises a highly hierarchical architecture and is composed of a nonmineral organic part, a predominantly type-I collagen, and a mineral inorganic part composed of hydroxyapatite (HA) nanocrystals (Ca(PO)(OH)). Although there has been extensive research indicating that the material properties of bone minerals affect metastatic breast cancer, it remains unclear how the microenvironment of the bone matrix, such as the roughness, which changes as a result of osteolytic bone remodeling, affects this disease. In this study, we created HA coatings in situ on polyelectrolyte multilayers (PEMs) by incubating PEMs in a mixture of phosphate and calcium ions. The HA films with distinctive roughness were successfully collected by controlling the incubation time, which served as the simulated microenvironment of the bone matrix. MDA-MB231 breast cancer cells were cultured on HA films, and an optimal roughness was observed in the adhesion, proliferation, and expression of two cytokines closely related to bone metastasis. This study contributed to the understanding of the effect of the microenvironment of the bone matrix, such as the roughness, on the metastasis behavior of breast cancer.
乳腺癌是一种常见的恶性肿瘤,起源于正常乳腺上皮组织。近 75%的晚期乳腺癌患者会发生骨转移,导致继发性肿瘤生长、溶骨性骨降解和预后不良。骨基质由高度分层的结构组成,由非矿化有机部分、主要为 I 型胶原和由羟基磷灰石 (HA) 纳米晶体 (Ca(PO)(OH)) 组成的矿化无机部分组成。尽管有大量研究表明骨矿物质的材料特性会影响转移性乳腺癌,但骨基质微环境(如由于溶骨性骨重塑而发生变化的粗糙度)如何影响这种疾病仍不清楚。在这项研究中,我们通过将 PEM 浸泡在磷酸盐和钙离子的混合物中,在聚电解质多层(PEM)上原位生成 HA 涂层。通过控制孵育时间成功收集了具有独特粗糙度的 HA 薄膜,该孵育时间用作骨基质的模拟微环境。MDA-MB231 乳腺癌细胞在 HA 薄膜上培养,与骨转移密切相关的两种细胞因子的粘附、增殖和表达观察到最佳粗糙度。这项研究有助于理解骨基质微环境(如粗糙度)对乳腺癌转移行为的影响。