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SDF-1 promotes metastasis of NSCLC by enhancing chemoattraction of megakaryocytes through the PI3K/Akt signaling pathway

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Abstract

Lung cancer (LC) is the leading cause of cancer-associated deaths worldwide, among which non-small-cell lung cancer (NSCLC) accounts for 80%. Stromal cell-derived factor-1 (SDF-1) inhibition results in a significant depletion of NSCLC metastasis. Additionally, SDF-1 is the only natural chemokine known to bind and activate the receptor CXCR4. Thus, we attempted to clarify the molecular mechanism of SDF-1 underlying NSCLC progression. Transwell migration, adhesion, and G-LISA assays were used to assess megakaryocytic chemotaxis in vitro and in vivo in terms of megakaryocytic migration, adherence, and RhoA activation, respectively. Western blotting was used to assess PI3K/Akt-associated protein abundances in MEG-01 cells and primary megakaryocytes under the indicated treatment. A hematology analyzer and flow cytometry were used to assess platelet counts in peripheral blood and newly formed platelet counts in Lewis LC mice under different treatments. Immunochemistry and flow cytometry were used to measure CD41+ megakaryocyte numbers in Lewis LC mouse tissue under different treatments. ELISA was used to measure serum TPO levels, and H&E staining was used to detect NSCLC metastasis. SDF-1 receptor knockdown suppressed megakaryocytic chemotaxis in Lewis LC mice. SDF-1 receptor inhibition suppressed megakaryocytic chemotaxis via the PI3K/Akt pathway. SDF-1 receptor knockdown suppressed CD41+ megakaryocyte numbers in vivo through PI3K/Akt signaling. SDF-1 receptor inhibition suppressed CD41+ megakaryocytes to hinder NSCLC metastasis. SDF-1 facilitates NSCLC metastasis by enhancing the chemoattraction of megakaryocytes via the PI3K/Akt signaling pathway, which may provide a potential new direction for seeking therapeutic plans for NSCLC.

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Author notes

  1. Yiguo Ai and Changhong Wan contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, China

    Yiguo Ai, Changhong Wan, Zijian Chen & Weizhe Huang

  2. Department of Cardiothoracic Surgery, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China

    Yansheng Wang

  3. Department of Respiratory and Critical Care Medicine, Shenzhen University General Hospital, Shenzhen, 518055, Guangdong, China

    Wen Zhao

Authors
  1. Yiguo Ai
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  2. Changhong Wan
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  3. Zijian Chen
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  4. Yansheng Wang
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  5. Wen Zhao
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  6. Weizhe Huang
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Correspondence to Weizhe Huang.

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This study was approved by the Ethics Committee of the Second Affiliated Hospital of Shantou University Medical College.

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Corresponding editor: Ramray Bhat

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Ai, Y., Wan, C., Chen, Z. et al. SDF-1 promotes metastasis of NSCLC by enhancing chemoattraction of megakaryocytes through the PI3K/Akt signaling pathway. J Biosci 49, 55 (2024). https://doi.org/10.1007/s12038-023-00393-9

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