Projects / Programmes
Lectins as modulators of anti-tumour immune response
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| T490 |
Technological sciences |
Biotechnology |
lectins, cancer, lymphocytes, proliferation, integrins, proteases
Researchers (16)
Organisations (2)
Abstract
Lectins are glycoproteins capable to bind specifically carbohydrates. They participate in numerous important physiological processes, they are able to modulate immune response and exhibit anti-tumour, anti-viral and insecticidal effects. Their activity is associated with cell adhesion, cell proliferation and induction of apoptosis, which are important mechanisms in development and progression of malignant diseases. Endogenous human lectins exhibit tumour promoting or tumour supressing functions and the level of their expression may serve for prediction of risk for cancer patients. However, exogenous plant and fungal lectins have exhibited strong anti-tumour activity and are used as anti-tumour drugs in complementary medicine. The most of so far exsisting studies have investigated the impact of lectins on proliferation of tumour cells and impairment of their invasiveness, nevertheless, the lectins have proved also modulation of T cell immune response, which is indispensable for regression of malignant disease. In this project we intend to isolate and characterize lectins from mushroom Clitocybe nebularis and from mistletoe (Viscum album). Isolated lectins will be tested with regard to their impact on proliferation of various tumour cells. Furthermore, we will evaluate their ability to stimulate T lymphocytes at coincident action of antigen presenting cells and tumour cells. During these processes the molecules with already known role in activation and proliferation of T lymphocytes, such as integrin receptors, proteases and adhesion molecules will be followed. Using differential analysis of gene expression, two dimensional electrophoresis, confocal microscopy and various immunochemical methods we will try to identify new molecules, being associated with the function of lectins. From our results we will assess whether plant and fungal lectins can stimulate anti-tumour immune response and serve as potential anti-tumour drugs.
Significance for science
The knowledge on glycosylation and the role of carbohydrates in cell signaling is rather poor. Lectins, capable of recognizing specific structures of carbohydrates, have an important role in various physiological processes and their irregular function is associated with the diseases such as cancer. To understand their function means also to know molecular mechanisms leading to pathological condition. In the case of immune response the lectins are capable of regulation of innate and adaptive response. Effectiveness of adaptive immune response is especially important for successful antitumour action. Basic mechanisms leading to the activation of the adaptive immune response are well known and are successfully used in the case of tumour vaccines. Less understood are the mechanisms enabling tumour cells to escape immune surveillance and the ways how to enhance adaptive immune response in patients with malignant diseases. In the latter lectins have appeared as promising factors, however, only understanding of their molecular functioning can justify their potential application in therapy. The results of this project have confirmed the expectations that the lectins are important regulators of immuneresponse. We demonstrated that also exogenous lectins may regulate these processes. With the knowledge on structure and mechanisms of action for some of the lectins we may change the specificity and regulate their action towards therapeutic targets, and improve the therapy of cancer and other, in particular immune diseases.
Significance for the country
Plants and fungi represent an important natural source of various lectins. They are already used in traditional medicine, their effectiveness is tested also in clinical studies on patients with cancer. Characterisation and understanding of individual lectins may improve their application in therapy of cancer patients and enable the preparation of drugs which will suit demands of registration authorities regarding their efficacy and safety. New knowledge on function and structure of lectins give us also an opportunity to prepare similar molecules with the methods of genetic engineering and the synthesis of small molecules mimicking the action of lectins, both interesting for pharmaceutical industry.
Our research provides an opportunity to prepare new pharmaceutical products for basic and complementary treatment, resulting in new added value, new companies and more employees. The new knowledge will be available to other researcher and provided to students during the education process at the university.
Most important scientific results
Annual report
2008,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
final report,
complete report on dLib.si
