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Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
SPP1 as a central mediator in the tumor microenvironment: Orchestrating cellular crosstalk, immune evasion, and
Linhong Wang1, Yachen Cheng1, Jialu Li1
1Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China; Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou 450052, Henan, China.
Abstract:
Secreted phosphoprotein-1 (SPP1) is a multifaceted glycoprotein that extends beyond its role as a mere component of the extracellular matrix, functioning instead as a pivotal signaling hub within the tumor microenvironment (TME). This review synthesizes current evidence regarding how SPP1 orchestrates a complex cellular network by mediating bidirectional crosstalk between cancer cells and key stromal components including cancer-associated fibroblasts, tumor-associated macrophages, endothelial cells, and lymphocytes. We elucidate how these interactions drive TME reprogramming, facilitating processes such as extracellular matrix remodeling, angiogenesis, immune evasion, and the establishment of therapeutic resistance to both chemotherapy and immunotherapy. Furthermore, we assess emerging therapeutic strategies targeting SPP1 such as aptamers and antibodies, highlighting their preclinical efficacy alongside the translational challenges that must be addressed. Ultimately, targeting the SPP1-mediated network represents a promising approach for dismantling the pro-tumorigenic TME and enhancing cancer treatment outcomes.
Insights
Secreted phosphoprotein-1 (SPP1) is a key signaling hub in the tumor microenvironment (TME). Targeting SPP1 interactions may overcome cancer's resistance to therapy and improve treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Secreted phosphoprotein-1 (SPP1) is a glycoprotein with crucial roles beyond the extracellular matrix.
- SPP1 acts as a central signaling hub within the tumor microenvironment (TME).
Purpose of the Study:
- To review the role of SPP1 in orchestrating cellular networks within the TME.
- To elucidate how SPP1-mediated crosstalk drives tumor progression and therapeutic resistance.
- To assess SPP1-targeting therapies for cancer treatment.
Main Methods:
- Literature review synthesizing current evidence on SPP1 function in the TME.
- Analysis of SPP1's role in mediating crosstalk between cancer cells and stromal components.
- Evaluation of preclinical data for SPP1-targeting therapeutic strategies.
Main Results:
- SPP1 mediates bidirectional crosstalk between cancer cells and stromal cells (fibroblasts, macrophages, endothelial cells, lymphocytes).
- These interactions promote TME reprogramming, including ECM remodeling, angiogenesis, immune evasion, and therapeutic resistance.
- Emerging SPP1-targeting therapies (aptamers, antibodies) show preclinical efficacy.
Conclusions:
- Targeting the SPP1-mediated network is a promising strategy to dismantle the pro-tumorigenic TME.
- Interfering with SPP1 signaling can enhance the efficacy of chemotherapy and immunotherapy.
- Addressing translational challenges is crucial for the clinical success of SPP1-targeted therapies.
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