Vnitr Lek 2009, 55(12):1145-1158

The complexity of interactions of the tumour growth process

Z. Valášková^1,*, S. Kiňová², Ľ. Danihel³, I. Ďuriš², D. Markovičová¹, B. Mravec^1,4, I. Hulín¹

¹ Oddelenie klinickej patofyziológie Ústavu patologickej fyziológie Lekárskej fakulty UK Bratislava, Slovenská republika, prednosta doc. MUDr. Marián Bernadič, CSc., mim. prof.

² I. interná klinika Lekárskej fakulty UK a FN Bratislava, Slovenská republika, prednostka doc. MUDr. Soňa Kiňová, PhD.

³ Ústav patologickej anatómie Lekárskej fakulty UK Bratislava, Slovenská republika, prednosta prof. MUDr. Ľudovít Danihel, CSc.

⁴ Ústav experimentálnej endokrinológie SAV Bratislava, Slovenská republika, riaditeľ prof. MUDr. Iwar Klimeš, DrSc.

It was believed for rather a long time that the only components of tumour tissue are transformed cells characterised by hyper-proliferation, invasivity and immortalisation. Therapeutic strategies thus focused on autonomous proliferation and tumour cell survival. These result from oncogene activation and inactivation of tumour-suppressor genes. Research studies showed that tumour growth itself is a complex process. In addition, studies confirmed involvement of heterotypical multicellular interactions in tumour tissue. Complexity as a characteristic is one of the processes that do not demonstrate attributes of linear systems. The process of tumour growth involves certain patterns that cannot be classified according to duration and sequence. Consequently, tumour growth can be viewed as a process with features typical for complexity. From this perspective, tumour environment consists of a range of cells, such as endothelial cells and their progenitor cells, pericytes, fibroblasts, tumour-associated fibroblasts, myofibroblasts, smooth muscle cells, mast cells, T- and B-lymphocytes, neutrophils, eosinophils, basophils, NK-cells and several different forms of macrophages. At present, well-founded assumptions exist that in-depth study of intra-tumour environment might lead to formulation of new principles in tumour biology as well as introduction of new therapeutic strategies. Research into details of tumour microenvironment is needed to expand scientific knowledge as well as to, subsequently, define tumour biomarkers. Monitoring of these biomarkers will facilitate molecular diagnostics. Biomarkers will be widely used to monitor tumour growth as well as to monitor the process of treatment. Monitoring of combinations of biomarkers will enable more detailed characterisation of tumour microenvironment. These might include, apart from receptors, signal molecules, growth factors and molecules accelerating apoptosis, specific molecules as well as their combinations or neoangiogenesis or tumour innervation parameters. Tumour complexity involves not just intracellular environment but also intracellular relationships and associations between cells and extracellular tumour components. Detection of circulating tumour cells represents another parameter to be monitored. Low-molecular weight fluorescent dyes will very likely be used for their detection. It can be assumed that circulating tumour cells will be used as markers of prognosis as well as indicators of malignity progression and treatment. Scientific advances in this area will facilitate individualised therapy of patients suffering from cancers. The aim of the present review study was to analyze scientific knowledge from the perspective of acceptance of complexity and heterogeneity of each tumour. We perceived processing of the vast amounts of literature as meaningful with respect to recognition of new knowledge and theoretical preparation for expected changes in diagnostics and treatment of tumours. We believe that the presented findings are a useful step towards achievement of comprehensive insight into tumour microenvironment.

Keywords: angiogenesis; tumour innervation; tumour microenvironment; vagus nerve; anti-inflammatory effects of nervous system

Received: March 25, 2009; Accepted: July 8, 2009; Published: December 1, 2009  Show citation