Konference: 2009 5. sympózium a workshop molekulární patologie a histo-cyto-chemie
Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie
Téma: Selected presentations
Číslo abstraktu: 014
Autoři: MUDr. Lukáš Lacina, Ph.D.; RNDr. Barbora Dvořánková, Ph.D.; prof. MUDr. Milan Kolář, Ph.D.; Ing. Hynek Strnad, Ph.D.; Prof. MUDr. Karel Smetana, DrSc.
Introduction: The role of stem cells in
cancer development and spreading has been established. As well
asnormal tissue stem cells, cancer stem cells also require a
special microenvi-ronment supporting their growth. Stromal
fibroblasts a.k.a. cancer-associated fibroblasts are important
components of the tumor stroma. The mutual interaction between
cancer cells and surrounding stromal fibroblasts is mediated
through direct cell-cell contacts and paracrine signals. Basal cell
carcinoma is the most common form of cancer of all with about a
million new cases estimated in the U.S. each year. This kind of
tumor can be locally aggressive, damaging the surrounding skin and
sometimes invading bone and cartilage. However the rate of
metastases is low.
Aim: This study reports on marker profiling changes of normal keratinocytes under the influence of mesenchymal cells derived from basal cell carcinoma in vitro, and especially on the induction of stem-cell-like features in affected epithelia. Material and methods: Weperformed a genomic search for up/ down-regulated genes for growth factors in stromal fibroblasts. We compared the phenotype of human tumors with an in vitro model where growth and phenotypic pattern of normal human keratinocytes were monitored under the influence of various types of fibroblasts including those prepared from stroma of basal cell carcinomas.
Results: We visualized a panel of keratins, endogenous lectins and binding sites for endogenous lectins, and markers of stem cells and growth factors which were upregulated. The observed epithelial cells in coculture subsequently expressed tumor markers as well as some putative stem cell markers.
Conclusion: Epithelial-mesenchymal interactions are of crucial importance in the course of malignant tumors, where stroma influence the behavior of the transformed epithelial cells. This biological activity can be attributed to the production of soluble paracrine factors and can be blocked by proper monoclonal antibodies. This observation can be of a great future therapeutical importance.
This study was supported by Ministry of Education Youth and Sport of the Czech Republic, projects No. MSM0021620806 and No. 1M0538.
Aim: This study reports on marker profiling changes of normal keratinocytes under the influence of mesenchymal cells derived from basal cell carcinoma in vitro, and especially on the induction of stem-cell-like features in affected epithelia. Material and methods: Weperformed a genomic search for up/ down-regulated genes for growth factors in stromal fibroblasts. We compared the phenotype of human tumors with an in vitro model where growth and phenotypic pattern of normal human keratinocytes were monitored under the influence of various types of fibroblasts including those prepared from stroma of basal cell carcinomas.
Results: We visualized a panel of keratins, endogenous lectins and binding sites for endogenous lectins, and markers of stem cells and growth factors which were upregulated. The observed epithelial cells in coculture subsequently expressed tumor markers as well as some putative stem cell markers.
Conclusion: Epithelial-mesenchymal interactions are of crucial importance in the course of malignant tumors, where stroma influence the behavior of the transformed epithelial cells. This biological activity can be attributed to the production of soluble paracrine factors and can be blocked by proper monoclonal antibodies. This observation can be of a great future therapeutical importance.
This study was supported by Ministry of Education Youth and Sport of the Czech Republic, projects No. MSM0021620806 and No. 1M0538.
Datum přednesení příspěvku: 24. 4. 2009
