Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling.
Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling.
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DOI：
10.1126/scisignal.abn4948
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发表时间：
2022-10-18
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
肿瘤微生物群越来越多地与癌症进展和对化疗的耐药性有关。在胰腺导管腺癌(PDAC)中，瘤内核梭杆菌的高负荷与患者较短的生存期有关。在这里，我们调查了这种联系背后的潜在机制。我们发现核孢子虫感染诱导正常胰腺上皮细胞和胰腺癌细胞分泌大量的细胞因子GM-CSFCXCL1、IL-8和MIP3α。这些细胞因子促进了感染和未感染的PDAC细胞的增殖、迁移和侵袭性细胞的运动，但在非癌胰腺上皮细胞中却没有，提示PDAC细胞的自分泌和旁分泌信号。值得注意的是，这种现象发生在对梭杆菌感染的反应中，而不考虑菌株，并且在没有免疫细胞和其他基质细胞的情况下发生。阻断GM-CSF信号明显限制了感染后的增殖收益。因此，胰腺中的核孢子虫感染诱导正常细胞和癌细胞分泌细胞因子，从而促进与肿瘤进展相关的PDAC细胞的表型。这些发现支持了探索胰腺癌宿主-微生物相互作用以指导未来治疗干预的重要性。
The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pancreatic ductal adenocarcinoma (PDAC), high intratumoral loads of Fusobacterium nucleatum correlate with shorter survival in patients. Here, we investigated the potential mechanisms underlying this association. We found that F. nucleatum infection induced both normal pancreatic epithelial cells and PDAC cells to secrete increased amounts of the cytokines GM-CSF, CXCL1, IL-8, and MIP-3α. These cytokines increased proliferation, migration, and invasive cell motility in both infected and noninfected PDAC cells but not in non-cancerous pancreatic epithelial cells, suggesting autocrine and paracrine signaling to PDAC cells. Notably, this phenomenon occurred in response to Fusobacterium infection regardless of the strain and in the absence of immune and other stromal cells. Blocking GM-CSF signaling markedly limited proliferative gains after infection. Thus, F. nucleatum infection in the pancreas elicits cytokine secretion from both normal and cancerous cells that promotes phenotypes in PDAC cells associated with tumor progression. The findings support the importance of exploring host-microbe interactions in pancreatic cancer to guide future therapeutic interventions.
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影响因子：
13.6
作者：
Datta R;Sivanand S;Lau AN;Florek LV;Barbeau AM;Wyckoff J;Skala MC;Vander Heiden MG
通讯作者：
Vander Heiden MG
影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
影响因子：
4.7
作者：
Du W;Pasca di Magliano M;Zhang Y
通讯作者：
Zhang Y
影响因子：
4.5
作者：
Chung M;Zhao N;Meier R;Koestler DC;Wu G;de Castillo E;Paster BJ;Charpentier K;Izard J;Kelsey KT;Michaud DS
通讯作者：
Michaud DS
影响因子：
5.7
作者：
Abed J;Maalouf N;Parhi L;Chaushu S;Mandelboim O;Bachrach G
通讯作者：
Bachrach G