Gadde Manasa, Mehrabi-Dehdezi Melika, Debeb Bisrat G, Woodward Wendy A, Rylander Marissa Nichole
Walker Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2023 Oct 8;15(19):4883. doi: 10.3390/cancers15194883.
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（IBC）是一种侵袭性疾病，预后较差且缺乏有效的治疗方法。人们普遍认为，了解肿瘤相关巨噬细胞（TAM）与肿瘤微环境之间的相互作用对于识别有助于预后和后续开发有效治疗方法的独特靶向标志物至关重要。在本研究中，我们展示了一个三维体外微流控IBC平台，该平台由THP1 M0、M1或M2巨噬细胞、IBC细胞和内皮细胞组成。该平台包括一个含有内皮化血管的胶原基质，为细胞相互作用创造了一个生理相关环境。通过利用这个平台，发现无论巨噬细胞表型如何，包含肿瘤相关巨噬细胞（TAM）都会导致新血管芽的形成增加和内皮通透性增强。有趣的是，与仅含有THP-1 M0和MDA-IBC3细胞的平台相比，含有THP-1 M1或M2巨噬细胞的平台在胶原细胞外基质（ECM）中表现出明显更大的孔隙率。细胞因子分析显示，当巨噬细胞在平台中培养时，IL-8和MMP9有选择性地增加。值得注意的是，仅在含有MDA-IBC3和M0巨噬细胞的平台中观察到肿瘤细胞向血管内的浸润。
