Journal Article

Human endogenous retroviruses and cancer prevention: evidence and prospects

Mastrangelo, Giuseppe, Vineis, Paolo, Palù, Giorgio, Cegolon, Luca, Salata, Cristiano, Weiderpass, Elisabete

2013

Overview

Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env -gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder and breast cancer. An amino acid sequence similar to HERV-K-MEL, recognized to cause a significant protective effect against melanoma, is shared by the antigenic determinants expressed by some vaccines such as BCG, vaccinia virus and the yellow fever virus. HERV-K are also reactivated in the majority of human breast cancers. Monoclonal and single-chain antibodies against the HERV-K Env protein recently proved capable of blocking the proliferation of human breast cancer cells in vitro, inhibiting tumor growth in mice bearing xenograft tumors. Summary A recent epidemiological study provided provisional evidence of how melanoma risk could possibly be reduced if the yellow fever virus vaccine (YFV) were received at least 10 years before, possibly preventing tumor initiation rather than culling melanoma cells already compromised. Further research is recommended to confirm the temporal pattern of this protection and eliminate/attenuate the potential role of relevant confounders as socio-economic status and other vaccinations. It appears also appropriate to examine the potential protective effect of YFV against other malignancies expressing high levels of HERV-K antigens, namely breast cancer, sarcoma, lymphoma and bladder cancer. Tumor immune-therapy, as described for the monoclonal antibodies against breast cancer, is indeed considered more complex and less advantageous than immune-prevention. Cellular immunity possibly triggered by vaccines as for YFV might also be involved in anti-cancer response, in addition to humoral immunity.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Amino acid sequence / Analysis / Animals / Antigenic determinants / Antigens / Antigens, Viral - immunology / BCG / Binding sites / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - prevention & control / Breast Neoplasms - virology / Cancer / Cancer prevention / Cancer Research / Cell proliferation / Colleges & universities / Confidence intervals / Culling / Debate / Deoxyribonucleic acid / Development and progression / Diets / DNA / DNA methylation / Endogenous retroviruses / Endogenous Retroviruses - classification / Endogenous Retroviruses - genetics / Endogenous Retroviruses - immunology / Endogenous Retroviruses - pathogenicity / Envelope protein / Environmental factors / Epidemiology / Family / Female / Fetuses / Gene expression / Gene Expression Regulation, Viral / Genes / Genetic aspects / Genetics / Genomes / Genomics / Health aspects / Health Promotion and Disease Prevention / Health sciences / HERV-K / Host-Pathogen Interactions / Humans / Hypotheses / Immune system / Immunity (cell-mediated) / Immunity (humoral) / Infection / Infections / Integration / Longevity / Lymphoma / Lymphomas / Male / Malignancy / Medicine/Public Health / Melanoma / Melanoma - prevention & control / Melanoma - virology / Monoclonal antibodies / Mutation / Neoplasms - epidemiology / Neoplasms - genetics / Neoplasms - immunology / Neoplasms - prevention & control / Neoplasms - virology / Obesity / Oncology / Ovarian cancer / Ovarian Neoplasms - prevention & control / Ovarian Neoplasms - virology / Physiological aspects / Prevention / Proteins / Retroviridae Infections - epidemiology / Retroviridae Infections - prevention & control / Retroviridae Infections - virology / Retrovirus / Retroviruses / Risk Factors / Sarcoma / Smoking / Surgical Oncology / Transfer RNA / Tumors / Urinary bladder / Vaccination / Vaccines / Vaccinia / Vaccinia virus / Viral vaccines / Viral Vaccines - therapeutic use / Virus Replication / Viruses / Xenografts / Yellow Fever - prevention & control / Yellow Fever - virology / Yellow Fever Vaccine - therapeutic use / Yellow fever virus / Yellow fever virus vaccine