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Molecular analysis of Annexin expression in cancer
Tobias Hein1,2, Peter H Krammer1, Heiko Weyd3
1Division of Immunogenetics, Tumour Immunology Program, German Cancer Research Centre, 69120, Heidelberg, Germany.
Background:
Uptake of apoptotic cells induces a tolerogenic phenotype in phagocytes and promotes peripheral tolerance. The highly conserved Annexin core domain, present in all members of the Annexin family, becomes exposed on the apoptotic cell-surface and triggers tolerogenic signalling in phagocytes via the Dectin-1 receptor. Consequently, Annexins exposed on tumour cells upon cell death are expected to induce tolerance towards tumour antigens, inhibiting tumour rejection.
Methods:
Expression analysis for all Annexin family members was conducted in cancer cell lines of diverse origins. Presentation of Annexins on the cell surface during apoptosis of cancer cell lines was investigated using surface washes and immunoblotting. Expression data from the GEO database was analysed to compare Annexin levels between malignant and healthy tissue.
Results:
Six Annexins at least were consistently detected on mRNA and protein level for each investigated cell line. AnxA1, AnxA2 and AnxA5 constituted the major part of total Annexin expression. All expressed Annexins translocated to the cell surface upon apoptosis induction in all cell lines. Human expression data indicate a correlation between immune infiltration and overall Annexin expression in malignant compared to healthy tissue.
Conclusions:
This study is the first comprehensive analysis of expression, distribution and presentation of Annexins in cancer.
Insights
Cancer cells expose Annexins on their surface during apoptosis, potentially promoting immune tolerance and hindering anti-tumor responses. This study comprehensively analyzes Annexin expression and presentation in various cancer types.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Apoptotic cell uptake by phagocytes induces immune tolerance.
- The Annexin core domain, exposed on apoptotic cells, signals through Dectin-1, promoting tolerance.
- Surface-exposed Annexins on tumor cells may inhibit anti-tumor immunity by inducing tolerance.
Purpose of the Study:
- To comprehensively analyze the expression, distribution, and presentation of Annexins in cancer cells.
- To investigate the role of Annexins in tumor cell apoptosis and potential immune evasion strategies.
Main Methods:
- Cancer cell line expression analysis (mRNA and protein) for all Annexin family members.
- Investigation of Annexin cell surface presentation during apoptosis using surface washes and immunoblotting.
- Analysis of human expression data from the GEO database to compare Annexin levels in malignant versus healthy tissues.
Main Results:
- Six or more Annexins were consistently detected at mRNA and protein levels in all investigated cancer cell lines.
- Annexin A1 (AnxA1), Annexin A2 (AnxA2), and Annexin A5 (AnxA5) were the predominant Annexins.
- All detected Annexins translocated to the cell surface upon apoptosis induction, and higher Annexin expression correlated with immune infiltration in malignant tissues.
Conclusions:
- This study provides the first comprehensive analysis of Annexin expression, distribution, and presentation in cancer.
- Annexin exposure on apoptotic cancer cells is a conserved phenomenon across diverse cancer types.
- Understanding Annexin presentation is crucial for developing novel cancer immunotherapies.
