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Updated: Aug 20, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Interference in melanoma CD248 function reduces vascular mimicry and metastasis
Cheng-Hsiang Kuo1, Ya-Fang Wu2, Bi-Ing Chang2
1International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan. 10102080@gs.ncku.edu.tw.
Background:
Tumor vascular mimicry is an emerging issue that affects patient survival while having no treatment at the current moment. Despite several factors implicated in vascular mimicry, little is known about stromal factors that modulate tumor microenvironment and shape malignant transformation. CD248, a type-I transmembrane protein dominantly expressed in stromal cells, mediates the interaction between cells and extracellular matrix proteins. CD248 protein expression is associated with the metastatic melanoma phenotype and promotes tumor progression in the stromal cells. This study aimed to explore the cell-autonomous effects of CD248 in melanoma vascular mimicry to aid cancer therapy development.
Methods:
Loss-of-function approaches in B16F10 melanoma cells were used to study the cell-autonomous effects of CD248 on cell adhesion, migration, proliferation, and vascular mimicry. A solid-phase binding assay was performed to identify the interaction between CD248 and fibronectin. Horizontal and vertical cell migration assays were performed to analyze cell migration activity, and cell-patterned network formation on Matrigel was used to evaluate vascular mimicry activity. Recombinant CD248 (rCD248) proteins were generated, and whether rCD248 interfered with melanoma CD248 functions was evaluated in vitro. An experimental lung metastasis mouse model was used to investigate the effect of rCD248 treatment in vivo.
Results:
CD248 protein expression in melanoma cells was increased by a fibroblast-conditioned medium. Knockdown of CD248 expression significantly decreased cell adhesion to fibronectin, cell migration, and vascular mimicry in melanoma cells. The lectin domain of CD248 was directly involved in the interaction between CD248 and fibronectin. Furthermore, rCD248 proteins containing its lectin domain inhibited cell adhesion to fibronectin and slowed down cell migration and vascular mimicry. Treatment with rCD248 protein could reduce pulmonary tumor burden, accompanied by a reduction in vascular mimicry in mice with melanoma lung metastasis.
Conclusion:
CD248 expression in melanoma cells promotes malignant transformation by increasing the activity of cell adhesion, migration, and vascular mimicry, whereas rCD248 protein functions as a molecular decoy interfering with tumor-promoting effects of CD248 in melanoma cells.
Insights
CD248 protein promotes melanoma progression by enhancing cell adhesion, migration, and vascular mimicry. Recombinant CD248 protein acts as a decoy, inhibiting these tumor-promoting effects and reducing metastasis.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Tumor vascular mimicry is a critical factor in patient survival with no current treatments.
- Stromal factors influencing the tumor microenvironment and malignant transformation are not well understood.
- CD248, a transmembrane protein in stromal cells, interacts with extracellular matrix and is linked to melanoma metastasis.
Purpose of the Study:
- To investigate the cell-autonomous role of CD248 in melanoma vascular mimicry.
- To explore CD248's impact on melanoma cell adhesion, migration, and proliferation.
- To assess the therapeutic potential of targeting CD248 in melanoma.
Main Methods:
- Loss-of-function studies using B16F10 melanoma cells to assess CD248 effects.
- Solid-phase binding assays to determine CD248-fibronectin interaction.
- In vitro and in vivo experiments using recombinant CD248 (rCD248) in a mouse model of melanoma lung metastasis.
Main Results:
- CD248 knockdown reduced melanoma cell adhesion to fibronectin, migration, and vascular mimicry.
- The lectin domain of CD248 is crucial for fibronectin interaction.
- rCD248 inhibited melanoma cell adhesion and migration, and reduced lung metastasis and vascular mimicry in vivo.
Conclusions:
- CD248 expression in melanoma cells drives malignant transformation through increased adhesion, migration, and vascular mimicry.
- rCD248 protein acts as a molecular decoy, counteracting CD248's pro-tumorigenic functions in melanoma.
- Targeting CD248 offers a potential therapeutic strategy for melanoma treatment.
