Inflammatory breast cancer (IBC) is an aggressive disease with a poor prognosis and a lack of effective treatments. It is widely established that understanding the interactions between tumor-associated macrophages (TAMs) and the tumor microenvironment is essential for identifying distinct targeting markers that help with prognosis and subsequent development of effective treatments. In this study, we present a 3D in vitro microfluidic IBC platform consisting of THP1 M0, M1, or M2 macrophages, IBC cells, and endothelial cells. The platform comprises a collagen matrix that includes an endothelialized vessel, creating a physiologically relevant environment for cellular interactions. Through the utilization of this platform, it was discovered that the inclusion of tumor-associated macrophages (TAMs) led to an increase in the formation of new blood vessel sprouts and enhanced permeability of the endothelium, regardless of the macrophage phenotype. Interestingly, the platforms containing THP-1 M1 or M2 macrophages exhibited significantly greater porosity in the collagen extracellular matrix (ECM) compared to the platforms containing THP-1 M0 and the MDA-IBC3 cells alone. Cytokine analysis revealed that IL-8 and MMP9 showed selective increases when macrophages were cultured in the platforms. Notably, intravasation of tumor cells into the vessels was observed exclusively in the platform containing MDA-IBC3 and M0 macrophages.
炎性乳腺癌是一种侵袭性强、预后不良且缺乏有效治疗手段的疾病。学界普遍认为，理解肿瘤相关巨噬细胞与肿瘤微环境之间的相互作用，对于识别有助于预后判断及后续有效疗法开发的特定靶向标志物至关重要。本研究构建了一种三维体外微流控炎性乳腺癌研究平台，该平台包含THP1 M0、M1或M2型巨噬细胞、炎性乳腺癌细胞及内皮细胞。平台采用包含内皮化血管的胶原基质，构建出模拟生理状态的细胞互作环境。通过该平台研究发现，无论巨噬细胞表型如何，肿瘤相关巨噬细胞的加入均会促进新生血管芽的形成并增强内皮通透性。值得注意的是，与仅含THP-1 M0巨噬细胞和MDA-IBC3细胞的平台相比，含有THP-1 M1或M2型巨噬细胞的平台在胶原细胞外基质中表现出显著更高的孔隙率。细胞因子分析显示，当巨噬细胞在平台中培养时，IL-8和MMP9呈现选择性升高。特别值得关注的是，仅在含有MDA-IBC3细胞与M0巨噬细胞的平台中观察到肿瘤细胞向血管内侵袭的现象。
肿瘤(癌症)患者之家