2. Academic Validation
  3. Retinoic Acid Inhibits Tumor-Associated Mesenchymal Stromal Cell Transformation in Melanoma

Retinoic Acid Inhibits Tumor-Associated Mesenchymal Stromal Cell Transformation in Melanoma

  • Front Cell Dev Biol. 2021 Apr 6;9:658757. doi: 10.3389/fcell.2021.658757.
Qi Lou 1 2 3,  Minyi Zhao 1,  Quanhui Xu 4 5,  Siyu Xie 4,  Yingying Liang 2 3,  Jian Chen 4,  Lisha Yuan 5,  Lingling Wang 6,  Linjia Jiang 4,  Lisha Mou 3,  Dongjun Lin 1,  Meng Zhao 1 2 4 5
Affiliations

Affiliations

  • 1 Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
  • 2 Shenzhen Lansi Institute of Artificial Intelligence in Medicine, Shenzhen, China.
  • 3 Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
  • 4 Sun Yat-sen Memorial Hospital, RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China.
  • 5 Key Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
  • 6 The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
PMID: 33889575 DOI: 10.3389/fcell.2021.658757
Abstract

Bone marrow mesenchymal stem/stromal cells (BMSCs) can be transformed into tumor-associated MSCs (TA-MSCs) within the tumor microenvironment to facilitate tumor progression. However, the underline mechanism and potential therapeutic strategy remain unclear. Here, we explored that interleukin 17 (IL-17) cooperating with IFNγ transforms BMSCs into TA-MSCs, which promotes tumor progression by recruiting macrophages/monocytes and myeloid-derived suppressor cells (MDSCs) in murine melanoma. IL-17 and IFNγ transformed TA-MSCs have high expression levels of myelocyte-recruiting chemokines (CCL2, CCL5, CCL7, and CCL20) mediated by activated NF-κB signaling pathway. Furthermore, retinoic acid inhibits NF-κB signaling, decreases chemokine expression, and suppresses the tumor-promoting function of transformed TA-MSCs by prohibiting the recruitment of macrophages/monocytes and MDSCs in the tumor microenvironment. Overall, our findings demonstrate that IL-17 collaborating with IFNγ to induce TA-MSC transformation, which can be targeted by RA for melanoma treatment.

Keywords

MSC; interferon-γ; interleukin-17; retinoic acid; tumor associated MSC; tumor microenvironment.

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