Translocation of Helicobacter hepaticus synergizes with myeloid-derived suppressor cells and contributes to breast carcinogenesis.
Translocation of Helicobacter hepaticus synergizes with myeloid-derived suppressor cells and contributes to breast carcinogenesis.
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肝螺杆菌易位与骨髓源性抑制细胞协同作用，促进乳腺癌发生
DOI：
10.1080/2162402x.2022.2057399
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发表时间：
2022
期刊：
影响因子：
7.2
通讯作者：
Fox JG
中科院分区：
文献类型：
--
作者：
Deng H;Muthupalani S;Erdman S;Liu H;Niu Z;Wang TC;Fox JG
微生物生态失调在肠道疾病的发生发展中起着重要作用。最近的研究表明肠道细菌和乳腺癌之间存在联系。在这里，我们报告说，雌性ApcMin/+小鼠感染肝螺杆菌表现出增加乳腺和小肠/大肠肿瘤负荷与未感染的同窝仔。H.在小肠/大肠、乳腺肿瘤和邻近淋巴结中检测到肝细胞DNA，表明存在迁移途径。CD 11b + Gr 1+骨髓源性抑制细胞（MDSC）浸润并表达高水平的Wnt，可能通过激活Wnt/β-catenin通路促进肿瘤发生。我们以前的研究表明，组氨酸脱羧酶（Hdc）标志着一个群体的骨髓偏向造血干细胞和粒细胞MDSC。由表达IL-17的肥大细胞和肿瘤组织分泌的细胞因子/趋化因子促进Hdc+ MDSC扩增并向乳腺肿瘤运输。从H.在受体ApcMin/+小鼠中，肝感染小鼠增加了外周血、肠系膜淋巴结、乳腺和淋巴结中MDSC的频率。H.肝癌引发的MDSC也增加了乳腺肿瘤的大小和数量。结果表明，H.肝细胞可以从肠道转移到乳腺组织，以促进MDSC的乳腺肿瘤发生。靶向细菌和MDSC可能有助于预防和治疗肠外癌症。缩略语：肝螺杆菌，Hh;骨髓源性抑制细胞，MDSC;组氨酸脱羧酶，Hdc;乳腺癌，BC; T调节性，TR;炎性肠病，IBD;荧光原位杂交，FISH;骨髓偏向性造血干细胞，MB-HSC;粒细胞MDSC，PMN-MDSC;脂多糖，LPS; Toll样受体，TLR;肥大细胞，MC;粒细胞-巨噬细胞集落刺激因子，GM-CSF;上皮-间充质转化，EMT;肠上皮细胞。
ABSTRACT Microbial dysbiosis plays an important role in the development of intestinal diseases. Recent studies suggest a link between intestinal bacteria and mammary cancer. Here, we report that female ApcMin/+ mice infected with Helicobacter hepaticus exhibited an increased mammary and small/large intestine tumor burden compared with uninfected littermates. H. hepaticus DNA was detected in small/large intestine, mammary tumors, and adjacent lymph nodes, suggesting a migration pathway. CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) infiltrated and expressed high levels of Wnts, likely enhancing tumorigenesis through activation of Wnt/β-catenin pathway. Our previous studies indicated that histidine decarboxylase (Hdc) marks a population of myeloid-biased hematopoietic stem cells and granulocytic MDSCs. Cytokines/chemokines secreted by IL-17-expressing mast cells and tumor tissues promoted Hdc+ MDSCs expansion and trafficking toward mammary tumors. Adoptive transfer of MDSCs isolated from H. hepaticus-infected mice increased MDSCs frequencies in peripheral blood, mesenteric lymph nodes, mammary gland, and lymph nodes in recipient ApcMin/+ mice. The adoptive transfer of H. hepaticus primed MDSCs also increased the size and number of mammary tumors. Our results demonstrate that H. hepaticus can translocate from the intestine to mammary tissues to promote mammary tumorigenesis with MDSCs. Targeting bacteria and MDSCs may be useful for the prevention and therapy of extraintestinal cancers. Abbreviations: Helicobacter hepaticus, Hh; myeloid-derived suppressor cell, MDSC; histidine decarboxylase, Hdc; Breast cancer, BC; T regulatory, TR; inflammatory bowel disease, IBD; fluorescence in situ hybridization, FISH; myeloid-biased hematopoietic stem cells, MB-HSCs; granulocytic MDSCs, PMN-MDSCs; Lipopolysaccharide, LPS; Toll-like receptors, TLRs; Mast cells, MCs; Granulocyte-macrophage colony-stimulating factor, GM-CSF; epithelial–mesenchymal transition, EMT; Intestinal epithelial cells, IECs.
影响因子：
4.6
作者：
Jacqueline C;Brazier L;Faugère D;Renaud F;Thomas F;Roche B
通讯作者：
Roche B