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Abstract：
The in vivo functions of SerpinB2 in tumor cells and tumor-associated macrophages (TAMs) during breast cancer development and metastasis remain elusive. SerpinB2-deficient MMTV-PyMT mice (PyMTSB2-/-) were previously produced to explore the biological roles of SerpinB2 in breast cancer. Compared with MMTV-PyMT wild-type (PyMTWT) mice, PyMTSB2-/- mice showed delayed tumor progression and reduced CK8 + tumor cell dissemination to lymph nodes. RNA-Seq data revealed significantly enriched genes associated with inflammatory responses, especially upregulated M1 and downregulated M2 macrophage marker genes in PyMTSB2-/- tumors. Decreased CD206+M2 and increased NOS2+M1 markers were detected in the primary tumors and metastatic lymph nodes of PyMTSB2-/- mice. In an in vitro study, SerpinB2 knockdown decreased the sphere formation and migration of MDA-MB-231 cells and suppressed protumorigenic M2 polarization of RAW264.7 cells. The combination of low SerpinB2, high NOS2, and low CD206 expression was favorable for survival in patients with breast cancer, as assessed in the BreastMark dataset. Our study demonstrates that SerpinB2 deficiency delays mammary tumor development and metastasis in PyMTWT mice, along with reduced sphere formation and migration abilities of tumor cells and decreased macrophage protumorigenic polarization.
摘要：
在乳腺癌发展和转移过程中，SerpinB2在肿瘤细胞和肿瘤相关巨噬细胞（TAM）中的体内功能仍然难以捉摸。SerpinB2缺陷型MMTV-PyMT小鼠（PyMTSB2-/-）先前被生产用于探索SerpinB2在乳腺癌中的生物学作用。与MMTV-PyMT野生型(PyMTWT)小鼠相比,PyMTSB2-/-小鼠显示延迟的肿瘤进展和减少的CK8+肿瘤细胞向淋巴结的播散。RNA-Seq数据显示，与炎症反应相关的基因显著富集，尤其是在PyMTSB2-/-肿瘤中上调M1和下调M2巨噬细胞标记基因。在PyMTSB2-/-小鼠的原发性肿瘤和转移性淋巴结中检测到CD206M2降低和NOS2M1标志物增加。在一项体外研究中，SerpinB2敲除降低MDA-MB-231细胞的球体形成和迁移，并抑制RAW264.7细胞的原瘤M2极化。低SerpinB2，高NOS2和低CD206表达的组合有利于乳腺癌患者的生存，如在BreastMark数据集中评估的。我们的研究表明，SerpinB2缺乏延迟PyMTWT小鼠乳腺肿瘤的发展和转移，随着肿瘤细胞球体形成和迁移能力的降低和巨噬细胞原瘤极化的降低。
