Basic FGF, EGF, and PDGF modify TGFβ-induction of smooth muscle cell phenotype in human prostatic stromal cells

Peehl, Donna M.; Sellers, Robert G.

doi:10.1002/(sici)1097-0045(19980501)35:2<125::aid-pros6>3.0.co;2-i

Cited by 37 publications

(28 citation statements)

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“…TGF-b1 stimulates synthesis of matrix components by fibroblasts, including collagen type I and promotes angiogenesis in wound repair granulation tissue (Roberts et al, 1986;Roberts and Sporn, 1996). In prostate stromal cells, TGF-b1 induced synthesis of collagen type I (Fukabori et al, 1997), fibronectin (Butter et al, 2001), tenascin (Tuxhorn et al, 2002c), versican (Sakko et al, 2001) and induced myodifferentiation (Peehl and Sellers, 1998;Tuxhorn et al, 2002a). TGF-b1 is overexpressed in many carcinomas, including prostate cancer epithelial cells (Eastham et al, 1995), and has been reported as a primary inducer of myofibroblast differentiation in reactive stroma fibroblasts (Desmouliere et al, 1993; TGF-b signaling in prostate cancer reactive stroma F Yang et al Tuxhorn et al, 2002a).…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma

2007

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Transforming growth factor-b (TGF-b) is overexpressed at sites of wound repair and in most adenocarcinomas including prostate cancer. In stromal tissues, TGF-b regulates cell proliferation, phenotype and matrix synthesis. To address mechanisms of TGF-b action in cancerassociated reactive stroma, we developed prostate stromal cells null for TGF-b receptor II (TbRII) or engineered to express a dominant-negative Smad3 to attenuate TGF-b signaling. The differential reactive stroma (DRS) xenograft model was used to evaluate altered stromal TGF-b signaling on LNCaP tumor progression. LNCaP xenograft tumors constructed with TbRII null or dominantnegative Smad3 stromal cells exhibited a significant reduction in mass and microvessel density relative to controls. Additionally, decreased cellular fibroblast growth factor-2 (FGF-2) immunostaining was associated with attenuated TGF-b signaling in stroma. In vitro, TGF-b stimulated stromal FGF-2 expression and release. However, stromal cells with attenuated TGF-b signaling were refractory to TGF-b-stimulated FGF-2 expression and release. Re-expression of FGF-2 in these stromal cells in DRS xenografts resulted in restored tumor mass and microvessel density. In summary, these data show that TGF-b signaling in reactive stroma is angiogenic and tumor promoting and that this effect is mediated in part through a TbRII/Smad3-dependent upregulation of FGF-2 expression and release.

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Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma

2007

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“…67,68,70,71,81,82 Often these media formulations contain additives to promote differentiation or proliferation. [81][82][83][84][85] Whatever the variations in media formulation, the resultant cultured prostatic stroma is generally a collection of fibroblasts, myofibroblasts and smooth muscle cells, somewhat reminiscent of the prostatic tissue of (mostly) ageing males. 75 The relative proportion of these cell types in native human prostatic stroma is still debatable and the data linking BPH with an increase of individual tissue components is not clear; for example, the connective tissue mass in hyperplastic prostates has been shown to increase 86,87 or to remain static.…”

Section: Cultured Cell Models Of Human Prostate Contractilitymentioning

confidence: 99%

“…Establish how steroid hormones and growth/differentiation factors (such as TGF-␤) affect function, because they are known to elevate markers of 'muscleness'. 77,78,83,85,107 3. Determine the regulatory role of epithelium upon stromal cell activity.…”

Section: Cultured Cell Models Of Human Prostate Contractilitymentioning

confidence: 99%

Current models of human prostate contractility

Haynes

Ventura

2005

Clin Exp Pharma Physio

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SUMMARY1. The human prostate is a compact gland contributing to seminal fluid. With increasing age, most humans will develop benign prostatic hyperplasia, a condition of prostatic enlargement and contractility that leads to occlusion of the urethra. Over many years, investigators have used a variety of animal and cell culture models to elucidate some of the contractile and proliferative mechanisms that may be associated with the development of this condition.2. This review briefly assesses the current state of knowledge of the mechanisms underlying human prostatic contractility and compares it with that of animal and cell culture models. It is not intended as a comprehensive methodological review, nor is it intended to indicate our preferences for either model. Our aim is to correlate findings from animal and cell culture models with the current understanding of human prostate contractility.3. We hope that the present review will increase awareness of the suitability of the current models in developing our understanding of benign prostatic hyperplasia.

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“…TGF-b1 stimulates synthesis of matrix components by fibroblasts, including collagen type I and promotes angiogenesis in wound repair granulation tissue Roberts and Sporn, 1996). In prostate stromal cells, TGF-b1 induced synthesis of collagen type I (Fukabori et al, 1997), fibronectin (Butter et al, 2001), tenascin (Tuxhorn et al, 2002c), versican (Sakko et al, 2001) and induced myodifferentiation (Peehl and Sellers, 1998;Tuxhorn et al, 2002a). TGF-b1 is overexpressed in many carcinomas, including prostate cancer epithelial cells , and has been reported as a primary inducer of myofibroblast differentiation in reactive stroma fibroblasts TGF-b signaling in prostate cancer reactive stroma F Yang et al Tuxhorn et al, 2002a).…”

Section: Discussionmentioning

confidence: 99%

Attenuated Transforming Growth Factor Beta Signaling as a Therapeutic for Prostate Cancer Progression

Yang¹

2008

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE 14-04-2008 REPORT TYPE Annual DATES COVERED FEB 2007 -31 JUL 2008 TITLE AND SUBTITLE Attenuated Transforming Growth Factor Beta 5a. CONTRACT NUMBERSignaling as a Therapeutic for Prostate Cancer Progression 5b. GRANT NUMBER DAMD W81XWH-07-1-0200 5c. PROGRAM ELEMENT NUMBER AUTHOR(S)Feng Yang, Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBEREmail: fyang@bcm.edu 5f. WORK UNIT NUMBER PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERBaylor College of Medicine Houston, TX 77025 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe purpose of this proposal is to determine the effects of stromal TGF-beta signaling inhibition by SD-208 (a TbetaRI-specific inhibitor) on prostate cancer growth, by using both in vitro prostate cancer/stromal cell co-culture model and in vivo xenograft model. In this initial funding year, we have tested the SD-208 efficiency in inhibiting TGF-beta signaling in prostate stromal cells. We further demonstrated that TGF-beta signaling in prostate stromal cells induced a complex response in prostate cancer cells. This response can be inhibited by either knockout of TbetaRII from mouse prostate stromal cells or by addition of SD-208 into the co-culture of human prostate cancer cells and human prostate stromal cells. We are using cDNA microarray and qPCR to identify the potential signaling molecules regulating these events. Based on these in vitro results, we are now carrying out the in vivo studies. We expect to finish all these studies at the conclusion of this award and present these sets of data in the final report. W81XWH-07-1-0200 "Attenuated Transforming Growth Factor Beta Signaling as a Therapeutic for Prostate Cancer Progression" SUBJECT TERMS Introduction:Our studies have defined reactive stroma in human prostate cancer progression (1). TGF-β is overexpressed in most carcinomas asso...

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Basic FGF, EGF, and PDGF modify TGFβ-induction of smooth muscle cell phenotype in human prostatic stromal cells

Cited by 37 publications

References 50 publications

Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma

Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma

Current models of human prostate contractility

Attenuated Transforming Growth Factor Beta Signaling as a Therapeutic for Prostate Cancer Progression

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