Pregnancy associated breast cancers (PABCs) exhibit increased aggressiveness and overall poorer survival. During lactation, changes take place in the breast tissue microenvironment that lead to increased macrophage recruitment and alterations in adipose stromal cells (ASC-Ls). The interaction of these cells in PABCs could play a role in the increased aggressiveness of these cancers. We utilized an in vitro co-culture model to recreate the interactions of ASC-Ls and macrophages in vivo. We performed qRT-PCR to observe changes in gene expression and cytokine arrays to identify transcriptional changes that result in an altered microenvironment. Additionally, functional assays were performed to further elicit how these changes affect tumorigenesis. The co-culture of ASC-Ls and macrophages altered both mRNA expression and cytokine secretion in a tumor promoting manner. Tumorigenic cytokines, such as IL-6, CXCL1, CXCL5, and MMP-9 secretion levels, were enhanced in the co-culture. Additionally, conditioned media from the co-culture elevated the tumor cell proliferation and angiogenic potential of endothelial cells. These finds indicate that the changes seen in the microenvironment of PABC, specifically the secretion of cytokines, play a role in the increased tumorigenesis of PABCs by altering the microenvironment to become more favorable to tumor progression.
妊娠相关乳腺癌（PABCs）表现出更强的侵袭性和总体较差的生存率。在哺乳期，乳腺组织微环境发生变化，导致巨噬细胞募集增加和脂肪基质细胞（ASC-Ls）发生改变。这些细胞在PABCs中的相互作用可能在这些癌症侵袭性增强中发挥作用。我们利用体外共培养模型重现了ASC-Ls和巨噬细胞在体内的相互作用。通过qRT-PCR观察基因表达变化，并采用细胞因子阵列分析识别导致微环境改变的转录变化。此外，通过功能实验进一步探究这些变化如何影响肿瘤发生。ASC-Ls与巨噬细胞的共培养以促肿瘤方式改变了mRNA表达和细胞因子分泌。共培养体系中促肿瘤细胞因子（如IL-6、CXCL1、CXCL5和MMP-9）的分泌水平显著提升。同时，共培养条件培养基增强了肿瘤细胞增殖能力和内皮细胞的血管生成潜能。这些发现表明，PABC微环境中的变化——特别是细胞因子的分泌——通过改变微环境使其更有利于肿瘤进展，从而在PABC肿瘤发生增强过程中发挥重要作用。
肿瘤(癌症)患者之家