The emerging significance of the tumor microenvironment: examples on importance of cell contacts and effector secretion

Konference: 2014 10. symposium a workshop molekulární patologie a histo(cyto)chemie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Přednášky pozvaných hostů III

Číslo abstraktu: 23

Autoři: MUDr. Ondřej Kodet; RNDr. Barbora Dvořánková, Ph.D.; Mgr. Pavol Szabo, Ph.D.; Dr. Hans-Joachim Gabius; Ing. Eliška Drobná Krejčí, Ph.D.; Ing. Hynek Strnad, Ph.D.; Michal Kolář, Ph.D.; MUDr. Lukáš Lacina, Ph.D.; Prof. MUDr. Miloš Grim, DrSc.; prof. Ing. Petr Dvořák, CSc.; Prof. MUDr. Karel Smetana jr., DrSc.

The increasing incidence of malignant melanoma and morta-lity prompt intense efforts to study tumor biology. The malignant cells of melanomas derive from normal melanocytes, mela- nocytes themselves developing from neural crest-originating precursors. These stem cells with capacity to generate new melanocytes remain in the bulge region of hair follicles up to the adult age. We here direct attention to interactions between tumor cells and cells in their microenvironment. Of interest, the early embryonic microenvironment is able to reverse the aggressive behavior of malignant cells isolated from advanced melanomas, cancer cells migrating and docking at sites typical for neural crest cells. Conditioned media from cultures of human embryonic stem cells and cancer-associated/normal fibroblasts are able to influence the phenotype of cells prepared from advanced tumors. Further cell types occurring in the melanoma niche are keratinocytes. The epidermis overlaying the nodular melanoma has a pseudohyperplastic character with aberrant expression of keratins but with a reduced proliferation activity. Malignant melanocytes or neural crest stem cells significantly influence the differentiation pattern of cocultured keratinocytes and partially reduce their proliferation activity. Potent effector proteins such as iL-8, CXCL-1, FGF-2, and VEGFA appear to play a role in the keratinocyte-melanoma cells crosstalk. Such an in- tercellular interplay in cancer may have a rather general character. in respective work, we previously observed that melanoma-associated fibroblasts are bioactive on breast cancer cells. Moreover, cytokine iL-8 and chemokine CXCL-1 are produced by cancer-as- sociated fibroblasts from squamous cell carcinoma and markedly influence the phenotype of epithelial cells. These insights into cellular communication mechanisms may serve as developing resource for a perspective to help taming malignancy. 


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Datum přednesení příspěvku: 25. 4. 2014