Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: An in vitro study

Abstract

Abstract. The role of stem cells in cancer formation and spreading has been established. As with normal tissue, the cancer stem cells need a special microenvironment to support their growth. This microenvironment may be represented by the tumor stroma. One of the possible ways of tumor stromal formation is the epithelial-mesenchymal transition of tumor epithelium. Following this mechanism, stromal cells must share the basic genetic alterations with the tumor 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 mouse TC-1 cells that were prepared by the introduction of human papillomavirus type 16 (HPV16) genes E6 and E7 to lung epithelial cells on the phenotype of normal human interfollicular and hair follicle keratinocytes. From this point of view, they may resemble stromal cells formed by the epithelial-mesenchymal transition of cells from HPV-induced squamous cell carcinoma. In contrast to 3T3 murine embryonic fibroblasts which were used as control cells, TC-1 cells influenced not only the size of the keratinocytes and the shape of their colonies, but also induced the expression of keratins 8 and 19 and vimentin. In conclusion, TC-1 cells exhibited a marked biological activity by influencing the behavior of the normal human follicular and intefollicular keratinocytes. This observation is compatible with the hypothesis that stromal cells play an important role in tumor progression and spreading.

Phenotypic characterization of human keratinocytes in coculture reveals differential effects of fibroblasts from benign fibrous histiocytoma (dermatofibroma) as compared to cells from its malignant form and to normal fibroblasts

“…This observation is corroborated by a practically absent coexpression of keratins with vimentin, a protein that defines the epithelialmesenchymal transition [17,38,39]. The difference between absence of keratin 19 in epidermis positioned over the tumor in BFH in situ and the positive signal from keratinocytes cocultured with fibroblasts prepared from this tumor can be due to differences in the environmental conditions in vitro and in situ, to which fibroblasts from MFH can contribute, similar to fibroblasts from the basal cell carcinoma [16].…”

The Head and Neck Squamous Cell Carcinoma Microenvironment as a Potential Target for Cancer Therapy

“…However, other cell types, including the hypothetical source in cancer cells per se after epithelial-mesenchymal transition, cannot be fully excluded as the source cells [14,15,16], assuming CAF derived from the cancer cells would carry the same genetic alterations or HPV-16 oncogenes. In vitro experiments demonstrated that lung epithelial cells transfected with HPV-16 genes E6 and E7 acquired the mesenchymal phenotype and exhibited remarkable biological effects on co-cultured keratinocytes that are phenotypically similar to cancer cells [17]. However, other experiments demonstrated that origination of CAF from cancer cells is not too probable [14].…”

Cancer Microenvironment: What Can We Learn from the Stem Cell Niche

“…Moreover, HPV16 transformed lung epithelial cells are oncogenic and they acquire typical fibroblastic phenotype. When cocultured with normal human keratinocytes, normal keratinocytes acquire features very similar to cancerous cells [ 85 ]. On the other hand, human cancer cells grafted to nu/nu mice form tumors with stroma containing exclusively fibroblasts of the mouse origin, as was demonstrated by use of human-specific anti-vimentin antibodies [ 86 ].…”