TGFα stimulates growth of skin papillomas by autocrine and paracrine mechanisms but does not cause neoplastic progression

To investigate the role of transforming growth factor α (TGFα) in tumor development, we introduced the human TGFα (hTGFα) cDNA into cultured primary mouse epidermal cells or papilloma cells using a replication‐defective retroviral vector and analyzed skin grafts constructed with such cells. Expressi...

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Veröffentlicht in:Molecular carcinogenesis 1988, Vol.1 (1), p.7-12
Hauptverfasser: Finzi, Eric, Kilkenny, Anne, Strickland, James E., Balaschak, Mike, Bringman, Timothy, Derynck, Rik, Aaronson, Stuart, Yuspa, Stuart H.
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container_end_page 12
container_issue 1
container_start_page 7
container_title Molecular carcinogenesis
container_volume 1
creator Finzi, Eric
Kilkenny, Anne
Strickland, James E.
Balaschak, Mike
Bringman, Timothy
Derynck, Rik
Aaronson, Stuart
Yuspa, Stuart H.
description To investigate the role of transforming growth factor α (TGFα) in tumor development, we introduced the human TGFα (hTGFα) cDNA into cultured primary mouse epidermal cells or papilloma cells using a replication‐defective retroviral vector and analyzed skin grafts constructed with such cells. Expression of the exogenous gene was confirmed by detection of hTGFα mRNA by northern RNA blot analysis, and the secreted hTGFα was measured by ELISA of culture supernatants. Tumor cells expressing hTGFα produced benign tumors (papillomas), which were 1.5‐ to 2‐fold larger than tumors of parental cells when tested as skin grafts on nude mice. Grafts of normal cells that expressed hTGFα 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 hTGFα‐producing papilloma cells combined with either normal epidermal cells or hTGFα‐producing epidermal cells yielded large tumors. Mixed grafts containing keratinocytes expressing hTGFα and parental papilloma cells also produced large tumors. While the tumor size was substantially increased by hTGFα 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 hTGFα 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.
doi_str_mv 10.1002/mc.2940010105
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Expression of the exogenous gene was confirmed by detection of hTGFα mRNA by northern RNA blot analysis, and the secreted hTGFα was measured by ELISA of culture supernatants. Tumor cells expressing hTGFα produced benign tumors (papillomas), which were 1.5‐ to 2‐fold larger than tumors of parental cells when tested as skin grafts on nude mice. Grafts of normal cells that expressed hTGFα 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 hTGFα‐producing papilloma cells combined with either normal epidermal cells or hTGFα‐producing epidermal cells yielded large tumors. Mixed grafts containing keratinocytes expressing hTGFα and parental papilloma cells also produced large tumors. 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Carcinog</addtitle><description>To investigate the role of transforming growth factor α (TGFα) in tumor development, we introduced the human TGFα (hTGFα) cDNA into cultured primary mouse epidermal cells or papilloma cells using a replication‐defective retroviral vector and analyzed skin grafts constructed with such cells. Expression of the exogenous gene was confirmed by detection of hTGFα mRNA by northern RNA blot analysis, and the secreted hTGFα was measured by ELISA of culture supernatants. Tumor cells expressing hTGFα produced benign tumors (papillomas), which were 1.5‐ to 2‐fold larger than tumors of parental cells when tested as skin grafts on nude mice. Grafts of normal cells that expressed hTGFα 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. 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identifier ISSN: 0899-1987
ispartof Molecular carcinogenesis, 1988, Vol.1 (1), p.7-12
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source Wiley Online Library - AutoHoldings Journals; MEDLINE
subjects Animals
autocrine
Blotting, Northern
Blotting, Southern
Cell Line
Disease Models, Animal
Keratins - biosynthesis
Keratins - genetics
Key words
Mice
Mice, Nude
Neoplasm Transplantation
Papilloma - genetics
Papilloma - pathology
RNA, Messenger - genetics
skin
Skin - metabolism
Skin Neoplasms - genetics
Skin Neoplasms - pathology
TGFα
Transfection
Transforming Growth Factors - biosynthesis
Transforming Growth Factors - genetics
Transforming Growth Factors - physiology
title TGFα stimulates growth of skin papillomas by autocrine and paracrine mechanisms but does not cause neoplastic progression
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