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Growth stimulation and tumor promotion in skin
Abstract:
Stimulation of epidermal growth in adult mouse skin can be induced by chemical agents, such as phorbol esters and other skin mitogens, or by mechanical means, such as skin massage and skin wounding. It leads to different kinds of epidermal hyperproliferation, according to interference with mechanisms of endogenous growth control (G1 chalone) and to mediation by endogenous regulatory factors (prostaglandins). Certain phorbol esters and skin wounding induce epidermal hyperproliferation and, in addition, a metaplastic process. Another property of these metaplasiogenic mitogens is their tumor-promoting efficacy in mouse skin, which has been initiated by a carcinogen in a subthreshold dose. Tailor-made phorbol esters allow the subdivision of the process of tumor promotion into two stages. In the first--probably irreversible--stage, a single application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or wounding brings about the events critical and obligatory for promotion, whereas in the second--probably reversible--stage, repetitive applications of an "incomplete promoter" evoke epidermal hyperplasia necessary to make the tumors visible. Adult guinea pig epidermis in vivo, as well as primary cell cultures derived from adult guinea pig ear epidermis, responds to the proliferative effects of phorbol esters such as TPA along a similar sequence of biochemical events as mouse skin in vivo. The in vitro approach allows the study of the molecular events involved in the mechanism of action of phorbol esters in more detail.
Insights
Skin growth can be stimulated by chemicals like phorbol esters or mechanical methods like wounding. These methods induce epidermal hyperproliferation and tumor promotion in mouse skin, with distinct stages identified.
Area of Science:
- Dermatology
- Oncology
- Cell Biology
Background:
- Epidermal growth stimulation in adult mouse skin can be triggered by chemical agents (e.g., phorbol esters) or mechanical stimuli (e.g., wounding).
- These stimuli can lead to epidermal hyperproliferation by interfering with growth control mechanisms and involving regulatory factors like prostaglandins.
- Certain agents, like phorbol esters and wounding, can also induce metaplasia and possess tumor-promoting efficacy in carcinogen-initiated mouse skin.
Purpose of the Study:
- To investigate the mechanisms of epidermal growth stimulation and tumor promotion induced by phorbol esters and skin wounding.
- To differentiate the stages involved in the two-stage process of tumor promotion.
- To compare the response of guinea pig epidermis in vivo and in vitro to phorbol esters.
Main Methods:
- Induction of epidermal hyperproliferation and metaplasia using phorbol esters and skin wounding in mouse models.
- Administration of carcinogens and tumor promoters to study the stages of tumor promotion.
- Culturing of adult guinea pig ear epidermis in vitro for comparative analysis.
- Biochemical analysis of cellular responses to phorbol esters.
Main Results:
- Phorbol esters and skin wounding induce epidermal hyperproliferation and metaplasia.
- Tumor promotion in mouse skin can be divided into two stages: an irreversible initiation stage and a reversible promotion stage.
- Adult guinea pig epidermis, both in vivo and in vitro, exhibits similar biochemical responses to phorbol esters as mouse skin.
Conclusions:
- Chemical and mechanical stimuli can effectively induce epidermal growth and hyperproliferation.
- The process of tumor promotion involves distinct, stage-specific events, with tailor-made phorbol esters aiding in their differentiation.
- In vitro models using guinea pig epidermis provide a detailed platform for studying the molecular mechanisms of phorbol ester action, mirroring in vivo responses.