TGFα stimulates growth of skin papillomas by autocrine and paracrine mechanisms but does not cause neoplastic progression
✍ Scribed by Eric Finzi; Anne Kilkenny; James E. Strickland; Mike Balaschak; Timothy Bringman; Rik Derynck; Stuart Aaronson; Stuart H. Yuspa
- Book ID
- 102944185
- Publisher
- John Wiley and Sons
- Year
- 1988
- Tongue
- English
- Weight
- 530 KB
- Volume
- 1
- Category
- Article
- ISSN
- 0899-1987
No coin nor oath required. For personal study only.
✦ Synopsis
To investigate the role of transforming growth factor a (TGFa) in tumor development, we introduced the human TGFa (hTGFcu) cDNA into cultured primary mouse epidermal cells or papilloma cells using a replicationdefective retroviral vector and analyzed skin grafts constructed with such cells. Expression of the exogenous gene was confirmed by detection of hTGFa mRNA by northern RNA blot analysis, and the secreted hTGFa was measured by ELISA of culture supernatants. Tumor cells expressing hTGFa produced benign tumors (papillomas), which were 1.5-t o 2-fold larger than tumors of parental cells when tested as skin grafts on nude mice. Grafts of normal cells that expressed hTGFa produced normal skin. When mixtures of parental tumor cells and normal mouse keratinocytes were grafted to nude mice, papilloma formation was suppressed and tumors that did form were small. Grafts of hTGFa-producing papilloma cells combined with either normal epidermal cells or hTGFaproducing epidermal cells yielded large tumors. Mixed grafts containing keratinocytes expressing hTGFa and parental papilloma cells also produced large tumors. While the tumor size was substantially increased by hTGFa expression, the tumors that developed in all groups were histologically benign and reached a stable size 4-5 wk after grafting. These results indicate that expression of hTGFcu by either tumor cells (autocrine) or adjoining normal cells (paracrine) can stimulate tumor growth, particularly when tumor growth is suppressed by normal tissue. However, expression of this growth factor did not appear to influence tumor progression directly.