HPV16 – transformed cells influence the phenotype of normal keratinocytes to stem cell-like character

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: 012

Autoři: RNDr. Barbora Dvořánková, Ph.D.; MUDr. Lukáš Lacina, Ph.D.; prof. MUDr. Vladimír Vonka, DrSc.; Prof. MUDr. Karel Smetana, DrSc.

Epidermal stem cells play a key role in epidermal self-renewal and healing processes. Hair follicles or the epidermal basal layer are the assumed sites for epidermal stem cells. As well as stem cells in normal tissue, cancer stem cells also require a special microenvironment to support their survival and growth. This microenvironment is represented by the tumor stroma which can also be formed by the epithelial-mesenchymal transition from tumor epithelial cells.

In an attempt to create a system capable of testing some aspects of the mesenchymal cell-keratinocyte interactions,we studied the effects of the fibroblastoid murine TC-1 cells on the phenotype of normal human interfollicular and hair follicle keratinocytes. TC-1 cells were prepared by the introduction of human papillomavirus type 16 (HPV16) genes E6 and E7 to murine embryonic lung epithelial cells. We used them as a model of stromal cells formed by the epithelialmesenchymal transition of cells from HPV-induced squamous cell carcinoma. 3T3 murine embryonic fibroblasts, routinely used for keratinocyte cultivation, were used as control cells.
Both 3T3 and TC1 cells were co-cultured with normal human follicular and intefollicular keratinocytes. To characterize the phenotype of co-cultured keratinocytes, we detected a panel
of keratins, nucleostemin, vimentin. When compared with 3T3 fibroblasts, TC-1 cells strongly influenced the size of keratinocytes,the shape of their colonies and their expression profile. In
co-cultured keratinocytes they induced expression of keratins 8 and 19 as well as vimentin.

In conclusion, TC-1 cells exhibited marked biological activity and they influenced the behaviour of the normal human follicular and intefollicular keratinocytes equally. This indicates that stromal cells play an important role in tumour progression and spreading.

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