| 초록 |
The ageing of population in developed counties brings many serious medical problems connected with age-related degenerative processes accumulated in population. The treatment of these patients needs new, not traditional solutions that represent the great challenge for the scientific community. This lecture shows how the study of intercellular crosstalk in cancer can be inspirative for regenerative medicine. Mutual interactions of distinct cell types in malignant tumors significantly influence biological properties of tumors including metastasation. Namely, the crosstalk between cancer-associated fibroblasts (CAF) and cancer cells is in the interest. CAF are usually rich for smooth muscle actin and from the cytological point of view they can be considered for myofibroblasts. Interestingly, the cells practically identical with CAF are also present in the wounds where they are responsible for wound contraction and they are also extensive producers of extracellular matrix and many important bioactive cytokines. Their similar activity was also described in cancer. CAF are originated from several cell types such as mesenchymal stem cells, endothelial cells, macrophages, pericytes and local fibroblasts. Transition of fibroblasts to CAF is stimulated by TGF-β1/3 and by endogenous lectin, galectins-1/3 with strong additive effect between both substances. The process of their formation can be inhibited by synthetic polyamines. Myofibroblasts prepared in vitro from human dermal fibroblasts produce 3-D networks of nanofibers of extracellular matrix (ECM) rich in fibronectin and galectin-1 with contribution of tenascin. When these lattices with networks of ECM were used for cultivation of human cells, their biological activity was ascertained. For example they stimulated transition of normal human keratinocytes to small cells rich in keratin 19, one of markers of epidermal stem cell. Similarly, these lattices stimulate the growth of endothelial cells including their ability to produce ECM. Galectin-1 introduced to the skin wound in the rat significantly facilitated the healing process. The presented results indicate the possibility of the use of lattices with ECM produced in vitro by CAF-like cells as biomaterial for tissue engineering. |
