Construction of artificial epithelial tissues prepared from human normal fibroblasts and C9 cervical epithelial cancer cells carrying human papillomavirus type 18 genes

Eun Kyung Yang, Seung Won Jin, Byung Tae Kang, Ik Hwan Kim, Jung Keug Park, Sang Sook Lee, Jin Woo Kim, Sue Nie Park

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


One cervical cancer cell line, C9, carrying human papillomavirus type 18 (HPV18) genes that is one of the major etiologic oncovirases for cervical cancer was characterized. This cell line was further characterized for its capacity related to the epithelial cell proliferation, stratification and differentiation in reconstituted artificial epithelial tissue. The in vitro construction of three dimensional artificial cervical epithelial tissue has been engineered using C9 epithelial cancer cells, human foreskin fibroblasts and a matrix made of type I collagen by organotypic culture of epithelial cells. The morphology of paraffin embedded artificial tissue was examined by histochemical staining. The artificial epithelial tissues were well developed having multilayer. However, the tissue morphology was similar to the cervical tissue having displasia induced by HPV infection. The characteristics of the artificial tissues were examined by determining the expression of specific marker proteins. In the C9 derived artificial tissues, the expression of EGF receptor, an epithelial proliferation marker proteins for stratum basale was observed up to the stratum spinosum. Another epithelial proliferation marker for stratum spinosum, cytokeratins 5/6/18, were observed well over the stratum spinosum. For the differentiation markers, the expression of involucrin and filaggrin were observed while the terminal differentiation marker, cytokeratins 10/13 were not detected at all. Therefore the reconstituted artificial epithelial tissues expressed the same types of differentiation marker proteins that are expressed in normal human cervical epithelial tissues but lacked the final differentiation capacity representing characteristics of C9 cell line as a cancer tissue derived cell line. Expression of HPV18 E6 oncoprotein was also observed in this artificial cervical epithelial tissue though the intensity of the staining was weak. Thus this artificial epithelial tissue could be used as a useful model system to examine the relationship between HPV-induced cervical oncogenesis and epithelial cell differentiation.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalBiotechnology and Bioprocess Engineering
Issue number1
Publication statusPublished - 1998

Bibliographical note

Funding Information:
Acknowledgement This work was supported in part by grants from Ministry of Science and Technology (FG1090 to S. Park) and Ministry of National Health and Welfare (BG150M to S. Park). We would like to thank Dr. Young Sook Son, Kyung Soo Hahm and Tae Ik Min for their technical advice and helps in many aspects.


  • Artificial epithelial tissue
  • Differentiation
  • Human papillomavirus (HPV) oncogenesis
  • Tissue engineering

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Biomedical Engineering


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