Interaction between Macrophages and Adipose Stromal Cells Increases the Angiogenic and Proliferative Potential of Pregnancy-Associated Breast Cancers.
Interaction between Macrophages and Adipose Stromal Cells Increases the Angiogenic and Proliferative Potential of Pregnancy-Associated Breast Cancers.
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DOI：
10.3390/cancers15184500
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发表时间：
2023-09-10
期刊：
影响因子：
5.2
通讯作者：
Mccready, Jessica
中科院分区：
文献类型：
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作者：
Doyle, Michael;Kwami, Noor;Joshi, Jaitri;Arendt, Lisa M.;Mccready, Jessica
在怀孕和哺乳期间确诊的乳腺癌(妊娠相关乳腺癌，PABC)比在生命中其他阶段确诊的乳腺癌更具侵袭性，存活率更低。先前的研究表明，哺乳期乳腺脂肪细胞的发育变化会促进肿瘤内血管的生长。这份报告的目的是确定肿瘤内的其他细胞是否与PABC的侵袭性有关。这里提供的数据表明，与哺乳期分离的脂肪细胞一起移植的肿瘤细胞增加了称为巨噬细胞的炎性细胞，并促进了小鼠乳腺中的肿瘤细胞生长。脂肪细胞和巨噬细胞在培养中的共同生长增加了因子的产生，从而增强了它们形成血管的能力。这些发现为PABC的侵袭性增加提供了解释，并提出了新的治疗途径。妊娠相关乳腺癌(PABC)表现出更强的侵袭性和总体较差的存活率。在哺乳期，乳房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-L)的改变。这些细胞在PABC中的相互作用可能在这些癌症的侵袭性增加中发挥作用。我们利用体外共培养模型来重建ASC-L和巨噬细胞在体内的相互作用。我们进行了qRT-PCR来观察基因表达和细胞因子阵列的变化，以确定导致微环境改变的转录变化。此外，还进行了功能分析，以进一步了解这些变化是如何影响肿瘤发生的。ASC-LS与巨噬细胞共培养后，可促进肿瘤细胞的基因表达和细胞因子的分泌。在共培养条件下，IL-6、CXCL1、CXCL5和基质金属蛋白酶-9等致瘤细胞因子的分泌水平均增强。此外，来自共培养的条件培养液提高了肿瘤细胞的增殖和内皮细胞的血管生成能力。这些发现表明，PABC微环境的变化，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的进展，在PABC的致瘤性增加中发挥了作用。
Breast cancer diagnosed during pregnancy and lactation (pregnancy-associated breast cancer, PABC) is more aggressive and has a decreased survival rate compared to breast cancers diagnosed at other stages in life. Previous research indicates that developmental changes to the fat cells in the mammary gland in lactation increase blood vessel growth within tumors. The aim of this report was to determine if other cells within the tumor contribute to PABC aggressiveness. Data presented here indicate that tumor cells transplanted with fat cells isolated during lactation increase inflammatory cells called macrophages and promote tumor cell growth in the mammary glands of mice. The growth of fat cells and macrophages together in a culture increases production of factors that enhance their ability to form blood vessels. These findings provide explanations for the increased aggressiveness of PABCs and suggest new treatment avenues. 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.
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