Cancer stromal fibroblasts as heterogeneous population?

Konference: 2012 8. Sympozium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Keynote lectures of invited speakers I.

Číslo abstraktu: 001

Autoři: Prof. MUDr. Karel Smetana jr., DrSc.; RNDr. Barbora Dvořánková, Ph.D.; Mgr. Pavol Szabo, Ph.D.; MUDr. Lukáš Lacina, Ph.D.; MUDr. Ondřej Kodet; Dr. Hans-Joachim Gabius; Ing. Hynek Strnad, Ph.D.; Michal Kolář, Ph.D.

Numerous results demonstrate that cancer cells need for their growth and spread through organism a specific microenvironment—the tumor stroma. Together with the tumor cells, the stroma forms a complex structure where intercellular interactions influence not only the structure but also the functional properties of the tumor. Thus the tumor can be considered a malignant organ. The stroma is composed of fibroblasts producing extracellular matrix and cytokines, infiltrating leukocytes, and blood/lymphatic vessels. The fibroblasts of the stroma—the cancer-associated fibroblasts (CAF)—are rich for smooth muscle actin. They produce actively molecules of extracellular matrix including the endogenous lectin galectin-1. We discovered that this galectin is also able to stimulate transition of normal fibroblasts to CAF. Interestingly, the extracellular matrix produced by CAF influences the differentiation status of co-cultured normal epithelial cells and facilitates wound closure. The CAF cocultured with epithelial cells are able to influence their phenotype. For example, CAF isolated from malignant tumors (squamous cell carcinoma, basal cell carcinoma, melanoma, and skin metastasis of breast cancer) are able to influence breast cancer cell line to more aggressive phenotype. When the phenotype of tested fibroblasts was evaluated, we observed significant differences including their ability of extracellular matrix production. These results indicate that the phenotypically different fibroblasts have very similar effect to cancer cell. These observations suggest the epithelial-mesenchymal interaction as a potential target of anticancer therapy influencing the tumor microenvironment as niche of cancer stem cell.


  1. Dvořánková et al.: Histochem. Cell Biol. DOI 10.1007/ s00418-012-0918-3 (2012)
  2. Dvořánková et al.: Cells Tissues Organs 194: 469–480 (2011)
  3. Lacina et al.: Int. Radiation. Biol. 83: 837–848 (2007)
  4. Lacina et al.: Brit. J. Dermatol. 156: 819–829 (2007)
  5. Plzák et al.: Anticancer Res. 30: 455–462 (2010)
  6. Smetana et al.: Oncol Rep. 20: 75–80 (2008)
  7. Strnad et al.: Histochem. Cell Biol. 133: 201–211 (2010)
  8. Szabo et al.: Biol. Cell 103: 233–248 (2011)
  9. Valach et al.: Int. J. Cancer in press (2012)

Datum přednesení příspěvku: 27. 4. 2012