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Updated: Sep 9, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
A Positive Feedback Loop Between SPP1 +Macrophages and Tumor Cells Promotes Head and Neck Squamous Cell Carcinoma
Chun Liu1, Chuwen Li1, Kun Wu1,2
1Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Background:
Emerging research has identified SPP1+macrophages as playing a critical role in head and neck squamous cell carcinoma (HNSCC). However, the specific mechanism by which SPP1+macrophages promote HNSCC progression remains poorly understood.
Methods:
The interaction of SPP1 and CD44 between SPP1+macrophages and tumor cells was detected by multiplex immunohistochemical staining of tissue sections, co-immunoprecipitation, and immunocytochemistry after co-culture. Flow cytometry, reverse transcription-polymerase chain reaction, and spheroid-formation assay were used to detect the stemness of tumor cells. Migration ability of tumor cells was analyzed by Transwell and wound-healing assays. In addition, the PI3K/Akt pathway was verified by western blot. The expression of soluble CD44 and SPP1 in serum was detected by enzyme-linked immunosorbent assay, and the expression of SPP1 in macrophages was detected by flow cytometry, western blot, and reverse transcription-polymerase chain reaction.
Results:
SPP1 and CD44 formed an interaction between SPP1+macrophages and tumor cells in HNSCC. SPP1+macrophages released SPP1 to regulate stemness and metastasis characteristics of tumor cells via the SPP1-CD44 axis. Soluble CD44 upregulated SPP1 expression in macrophages and thus, SPP1 and CD44 formed a positive feedback loop between SPP1+macrophages and tumor cells in HNSCC.
Conclusions:
SPP1-CD44 upregulates stemness and migration abilities of tumor cells in HNSCC. SPP1-CD44 forms an interaction and a positive feedback loop in SPP1+macrophages and tumor cells in HNSCC.
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