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Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

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Abstract

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-specific, thymic peptides comprise an effective group of regulators, mediating important immune functions. Thymosin fraction five (TFV) was the first thymic extract shown to stimulate lymphocyte proliferation and differentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin α (proTα) and thymosin α1 (Tα1) showed that they are of clinical significance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeficiencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their effect are yet not fully elucidated, proTα and Tα1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proTα, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of Tα1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proTα into the clinical setting.

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Abbreviations

AAK cells:

Anti-CD3-activated killer cells

BRM:

Biologic response modifier

CDDP:

Cisplatin

CML:

Cell-mediated lympholysis

CTL:

Cytotoxic T lymphocyte(s)

CY:

Cyclophosphamide

DC:

Dendritic cell(s)

DL:

Dalton’s lymphoma

DTIC:

Dacarbazine

5-FU:

5-Fluorouracil

HMGB1:

High mobility group box 1

HSP:

Heat sock protein

IFN:

Interferon

IL:

Interleukin

LAK cells:

Lymphokine-activated killer cells

3LL carcinoma:

Lewis lung carcinoma

MHC:

Major histocompatibility complex

NK cells:

Natural killer cells

NSCL cancer:

Non-small cell lung cancer

pI:

Isoelectric point

PBL:

Peripheral blood lymphocyte(s)

PBMC:

Peripheral blood mononuclear cell(s)

PGE2:

Prostaglandin E2

PMN:

Polymorphonuclear(s)

ProTα:

Prothymosin alpha

s.c.:

Subcutaneous

TACE:

Transarterial chemoembolization

TAM:

Tumor-associated macrophages

Tα1:

Thymosin alpha 1

Tβ4:

Thymosin beta 4

TFV:

Thymosin fraction V

TLR:

Toll-like receptor(s)

TNF:

Tumor necrosis factor

VP-16:

Etoposide

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Acknowledgments

We thank Dr. Margarita Skopeliti for compiling the figure and critically reading the manuscript. Co-financed by: the European Union (European Social Fund—ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)—Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund (to K.I.); the Hellenic State Scholarship Foundation (IKY) and the Deutscher Akademischer Austauschdienst (DAAD), IKYDA 61/2003 and IKYDA 165/2010; the European Union FP7 Capacities grant REGPOT-CT-2011-284460, INsPiRE; NATO SfP Project 982838; “GERONTOSHIELD” (BMBF Project 0315890F).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Animal and Human Physiology, Faculty of Biology, University of Athens, Panepistimiopolis, 15784, Athens, Greece

    Kyriaki Ioannou, Pinelopi Samara & Ourania E. Tsitsilonis

  2. Immunopeptide Chemistry Lab, Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research “Demokritos”, Patriarchou Gregoriou and Neapoleos, Aghia Paraskevi, 15310, Athens, Greece

    Evangelia Livaniou

  3. Tübingen Ageing and Tumour Immunology Group, Center for Medical Research, University of Tübingen Medical School, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Evelyna Derhovanessian

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  1. Kyriaki Ioannou
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  2. Pinelopi Samara
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  5. Ourania E. Tsitsilonis
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Correspondence to Ourania E. Tsitsilonis.

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Ioannou, K., Samara, P., Livaniou, E. et al. Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy. Cancer Immunol Immunother 61, 599–614 (2012). https://doi.org/10.1007/s00262-012-1222-8

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