Hedgehog Signaling Promotes Prostate Xenograft Tumor Growth (original) (raw)

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4Northwestern University Feinberg School of Medicine (L.F., W.C., R.La., M.L.G.L.), Chicago, Illinois 60611

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1 Curis, Inc. (C.V.P., C.C.D., J.L.Z.), Oncology Group, Cambridge, Massachusetts 02163

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1 Curis, Inc. (C.V.P., C.C.D., J.L.Z.), Oncology Group, Cambridge, Massachusetts 02163

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4Northwestern University Feinberg School of Medicine (L.F., W.C., R.La., M.L.G.L.), Chicago, Illinois 60611

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1 Curis, Inc. (C.V.P., C.C.D., J.L.Z.), Oncology Group, Cambridge, Massachusetts 02163

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4Northwestern University Feinberg School of Medicine (L.F., W.C., R.La., M.L.G.L.), Chicago, Illinois 60611

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2Division of Urology/Department of Surgery (J.G., A.S., A.M., R.Li., W.B.), University of Wisconsin, Madison, Wisconsin 53792

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2Division of Urology/Department of Surgery (J.G., A.S., A.M., R.Li., W.B.), University of Wisconsin, Madison, Wisconsin 53792

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4Northwestern University Feinberg School of Medicine (L.F., W.C., R.La., M.L.G.L.), Chicago, Illinois 60611

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2Division of Urology/Department of Surgery (J.G., A.S., A.M., R.Li., W.B.), University of Wisconsin, Madison, Wisconsin 53792

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Received:

23 January 2004

Published:

01 August 2004

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Lian Fan, Carmen V. Pepicelli, Christian C. Dibble, Winnie Catbagan, Jodi L. Zarycki, Robert Laciak, Jerry Gipp, Aubie Shaw, Marilyn L. G. Lamm, Alejandro Munoz, Robert Lipinski, J. Brantley Thrasher, Wade Bushman, Hedgehog Signaling Promotes Prostate Xenograft Tumor Growth, Endocrinology, Volume 145, Issue 8, 1 August 2004, Pages 3961–3970, https://doi.org/10.1210/en.2004-0079
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Abstract

During fetal prostate development, Sonic hedgehog (Shh) expression by the urogenital sinus epithelium activates Gli-1 expression in the adjacent mesenchyme and promotes outgrowth of the nascent ducts. Shh signaling is down-regulated at the conclusion of prostate ductal development. However, a survey of adult human prostate tissues reveals substantial levels of Shh signaling in normal, hyperplasic, and malignant prostate tissue. In cancer specimens, the Shh expression is localized to the tumor epithelium, whereas Gli-1 expression is localized to the tumor stroma. Tight correlation between the levels of Shh and Gli-1 expression suggests active signaling between the tissue layers. To determine whether _Shh_-Gli-1 signaling could be functionally important for tumor growth and progression, we performed experiments with the LNCaP xenograft tumor model and demonstrated that: 1) Shh expressed by LNCaP tumor cells activates Gli-1 expression in the tumor stroma, 2) genetically engineered Shh overexpression in LNCaP cells leads to increased tumor stromal Gli-1 expression, and 3) Shh overexpression dramatically accelerates tumor growth. These data suggest that hedgehog signaling from prostate cancer cells to the stroma can elicit the expression of paracrine signals, which promote tumor growth.

Copyright © 2004 by The Endocrine Society

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