PMID- 34207850
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210705
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 12
DP  - 2021 Jun 9
TI  - Salmonella Impacts Tumor-Induced Macrophage Polarization, and Inhibits 
      SNAI1-Mediated Metastasis in Melanoma.
LID - 10.3390/cancers13122894 [doi]
LID - 2894
AB  - Targeting metastasis is a vital strategy to improve the clinical outcome of 
      cancer patients, specifically in cases with high-grade malignancies. Here, we 
      employed a Salmonella-based treatment to address metastasis. The potential of 
      Salmonella as an anticancer agent has been extensively studied; however, the 
      mechanism through which it affects metastasis remains unclear. This study found 
      that the epithelial-to-mesenchymal transition (EMT) inducer SNAI1 was markedly 
      reduced in Salmonella-treated melanoma cells, as revealed by immunoblotting. 
      Furthermore, wound healing and transwell assays showed a reduced in vitro cell 
      migration following Salmonella treatment. Transfection experiments confirmed that 
      Salmonella acted against metastasis by suppressing protein kinase B 
      (Akt)/mammalian target of rapamycin (mTOR) signaling, which in turn inhibited 
      SNAI1 expression. Since it is known that metastasis is also influenced by 
      inflammation, we partly characterized the immune infiltrates in melanoma as 
      affected by Salmonella treatment. We found through tumor-macrophage co-culture 
      that Salmonella treatment increased high mobility group box 1 (HMGB1) secretion 
      in tumors to coax the polarization of macrophages in favor of an M1-like 
      phenotype, as shown by increased inducible nitric oxide synthase (iNOS) 
      expression and Interleukin 1 Beta (IL-1beta) secretion. Data from our animal study 
      corroborated the in vitro findings, wherein the Salmonella-treated group obtained 
      the lowest lung metastases, longer survival, and increased iNOS-expressing immune 
      infiltrates.
FAU - Pangilinan, Christian R
AU  - Pangilinan CR
AUID- ORCID: 0000-0003-3913-7912
AD  - Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 
      80424, Taiwan.
FAU - Wu, Li-Hsien
AU  - Wu LH
AD  - Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 
      80424, Taiwan.
FAU - Lee, Che-Hsin
AU  - Lee CH
AUID- ORCID: 0000-0002-8543-3862
AD  - Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 
      80424, Taiwan.
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung 40402, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20210609
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8230152
OTO - NOTNLM
OT  - Salmonella-mediated tumor therapy
OT  - macrophage polarization
OT  - melanoma
OT  - metastasis
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/03 06:00
MHDA- 2021/07/03 06:01
PMCR- 2021/06/09
CRDT- 2021/07/02 01:32
PHST- 2021/05/06 00:00 [received]
PHST- 2021/06/04 00:00 [revised]
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/07/02 01:32 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/07/03 06:01 [medline]
PHST- 2021/06/09 00:00 [pmc-release]
AID - cancers13122894 [pii]
AID - cancers-13-02894 [pii]
AID - 10.3390/cancers13122894 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Jun 9;13(12):2894. doi: 10.3390/cancers13122894.