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CD40 antigen is expressed by endothelial cells and tumor cells in Kaposi's sarcoma
J Pammer1, A Plettenberg, W Weninger
1Institute of Clinical Pathology, University of Vienna Medical School, Austria.
Insights
CD40 antigen is expressed on Kaposi
Area of Science:
- Immunology and Oncology
- Cell Biology and Signaling
Background:
- The CD40 antigen, a member of the tumor necrosis factor receptor superfamily, plays a role in cell proliferation, differentiation, and survival.
- Kaposi's sarcoma is a neoplasm associated with HHV-8 infection, often seen in HIV-1 seropositive individuals.
Purpose of the Study:
- To investigate the expression of the CD40 antigen on Kaposi's sarcoma spindle cells and endothelial cells.
- To explore the role of CD40 expression in the pathogenesis of Kaposi's sarcoma.
Main Methods:
- Immunohistochemistry was used to detect CD40 expression on tumor cells and vascular endothelium.
- Western blot analysis was performed on tumor lysates to identify CD40.
- In vitro cell cultures and interferon-gamma treatment were used to study CD40 regulation.
Main Results:
- CD40 was expressed on CD31- and CD34-positive Kaposi's sarcoma spindle cells in all tested tumors.
- CD40 was also found on vascular endothelial cells in tumor areas and inflammatory lesions, but not typically on lymphatic endothelium or normal skin endothelium.
- Interferon-gamma treatment up-regulated CD40 surface expression on Kaposi's sarcoma spindle cells.
Conclusions:
- CD40 antigen expression is up-regulated on endothelial cells during tissue inflammation.
- The presence of CD40 on Kaposi's sarcoma tumor cells may contribute to the neoplasm's pathogenesis by promoting cell survival.
Abstract:
The CD40 antigen is a member of the tumor necrosis factor receptor/nerve growth factor receptor superfamily and is involved in cell proliferation, differentiation, and survival. Using different monoclonal antibodies, we found CD40 expression by immunohistochemistry on CD31- and CD34-positive Kaposi's sarcoma spindle cells in all tumors of 18 HIV-1 seropositive and 4 HIV-1 seronegative patients. Western blot analysis of tumor lysates detected a 48- to 50-kd glycoprotein corresponding to the CD40 antigen expressed by B lymphocytes. CD40 expression was also detectable in one of four cultures of spindle cells derived from Kaposi sarcoma tissue. Treatment of the CD40-positive spindle cells but not of the CD40-negative ones with interferon-gamma up-regulated CD40 surface expression. Besides on Kaposi sarcoma tumor cells, CD40 was distinctly present on vascular endothelial cells in areas within and adjacent to the tumors and in benign inflammatory lesions such as granulation tissue of HIV-1-negative patients. In contrast, CD34-negative endothelia of thin walled vessels, most likely lymphatics, were predominantly CD40 negative. Only faint or no CD40 expression was found on endothelial cells in normal skin. We conclude from our data that expression of the CD40 antigen by endothelial cells is up-regulated during tissue inflammation. As signaling through CD40 is able to increase cell survival, expression of CD40 by Kaposi sarcoma tumor cells might play an important role in the pathogenesis of this neoplasm.