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Soluble ICAM-1 in breast cancer: clinical significance and biological implications
W J Köstler1, S Tomek, T Brodowicz
1Department of Medicine I, University Hospital, Vienna, Austria.
Objectives:
In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecule I (ICAM-1) on both tumour cells and antigen-presenting cells derived from patients with breast cancer, resulting in an abrogation of antigen presentation and tumour cell lysis. Recently, increased levels of a soluble isoform of ICAM-1 (sICAM-1) have been detected in the sera of breast cancer patients. The present investigation was performed in order to investigate the biological relevance of serum concentrations and the effects of sICAM-1 in patients with breast cancer.
Patients And Methods:
sICAM-1 was determined using a sandwich enzyme immunoassay on sera from 88 patients with various stages of breast cancer and correlated with clinical parameters. The effect of sICAM-1 present in the sera of patients with breast cancer upon unspecific and anti-Her-21/neu antibody-mediated cytotoxicity (ADCC), as well as upon antigen presentation, was determined using a 51Cr-release assay and [3H]thymidine-uptake of T cells after co-incubation with tetanus-toxoid-pulsed antigen-presenting cells.
Results:
In patients with early breast cancer, serum levels of sICAM-1 were significantly lower compared to patients with metastatic disease, but did not correlate with usual clinical parameters. In patients with metastatic breast cancer, a significant correlation of sICAM-1 with tumour markers CEA and CA 15-3 was observed. No influence of sICAM-1 upon unspecific cytotoxicity, ADCC, or the ability to present antigen was observed.
Discussion:
The origin of sICAM-1 in the sera of patients with breast cancer remains unknown. In contrast to its membrane-bound isoform, sICAM-1 was increased in the sera of patients with various stages of breast cancer, but its presence did not influence unspecific cytotoxicity, ADCC, or antigen-induced T cell proliferation.
Insights
Serum soluble intercellular adhesion molecule-1 (sICAM-1) is elevated in breast cancer patients, particularly those with metastatic disease. However, sICAM-1 did not impact immune responses like cytotoxicity or antigen presentation in this study.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Decreased membrane-bound ICAM-1 expression on tumor cells and antigen-presenting cells in breast cancer patients impairs immune responses.
- Increased soluble ICAM-1 (sICAM-1) levels have been observed in breast cancer patients' sera.
Purpose of the Study:
- To investigate the biological relevance of serum sICAM-1 concentrations in breast cancer patients.
- To determine the effects of sICAM-1 on immune functions such as antigen presentation and cytotoxicity.
Main Methods:
- Quantified sICAM-1 in 88 breast cancer patients' sera using enzyme immunoassay.
- Assessed the impact of sICAM-1 on antibody-dependent cell-mediated cytotoxicity (ADCC) and antigen presentation using cytotoxicity assays and T cell proliferation assays.
Main Results:
- Serum sICAM-1 levels were lower in early breast cancer than in metastatic disease but did not correlate with standard clinical parameters.
- In metastatic breast cancer, sICAM-1 correlated significantly with tumor markers CEA and CA 15-3.
- sICAM-1 did not influence unspecific cytotoxicity, ADCC, or antigen presentation capabilities.
Conclusions:
- The origin of elevated sICAM-1 in breast cancer patients' sera remains unclear.
- Despite increased levels in various stages of breast cancer, sICAM-1 did not affect key immune functions like cytotoxicity or T cell proliferation.