Keratinocyte Growth Factor Causes Proliferation of Urothelium In Vivo

Yi, Eunhee S.; Shabaik, Ahmed; Lacey, David L.; Bedoya, Adriana; Su, Yin; Housley, Regina M.; Danilenko, Dimitry M.; Benson, William G.; Cohen, Arthur M.; Pierce, Glenn F.; Thomason, Arlen; Ulich, Thomas R.

doi:10.1016/s0022-5347(01)66930-1

Cited by 80 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, the urothelium of FGF-7-null mice showed a profound reduction in thickness compared to wild type tissue, that results from the absence of intermediate cell layers [56]. In addition, FGF-7 is mitogenic for urothelial cells and appears to retard the maturation of urothelial cells to a terminally differentiated phenotype [57, 58]. …”

Section: Cell Surface Receptor Pathways Implicated In Urothelial Diffmentioning

confidence: 99%

When urothelial differentiation pathways go wrong: Implications for bladder cancer development and progression

DeGraff

Cates

Mauney

et al. 2013

Urologic Oncology: Seminars and Original Investigations

View full text Add to dashboard Cite

Differentiation is defined as the ability of a cell to acquire full functional behavior. For instance, the function of bladder urothelium is to act as a barrier to the diffusion of solutes into or out of the urine after excretion by the kidney. The urothelium also serves to protect the detrusor muscle from toxins present in stored urine. A major event in the initiation and progression of bladder cancer is loss of urothelial differentiation. This is important because less differentiated urothelial tumors (higher histologic tumor grade) are typically associated with increased biologic and clinical aggressiveness. The differentiation status of urothelial carcinomas can be assessed by histopathologic examination and is reflected in the assignment of a histologic grade (low-grade or high-grade). Although typically limited to morphologic evaluation in most routine diagnostic practices, tumor grade can also be assessed using biochemical markers. Indeed, current pathological analysis of tumor specimens is increasingly reliant on molecular phenotyping. Thus, high priorities for bladder cancer research include identification of (1) biomarkers that will enable the identification of high grade T1 tumors that pose the most threat and require the most aggressive treatment; (2) biomarkers that predict the likelihood that a low grade, American Joint Committee on Cancer stage pTa bladder tumor will progress into an invasive carcinoma with metastatic potential; (3) biomarkers that indicate which pTa tumors are most likely to recur, thus enabling clinicians to prospectively identify patients who require aggressive treatment; and (4) how these markers might contribute to biological processes that underlie tumor progression and metastasis, potentially through loss of terminal differentiation. This review will discuss the proteins associated with urothelial cell differentiation, with a focus on those implicated in bladder cancer, and other proteins that may be involved in neoplastic progression. It is hoped that ongoing discoveries associated with the study of these differentiation-promoting proteins can be translated into the clinic to positively impact patient care.

show abstract

Section: Cell Surface Receptor Pathways Implicated In Urothelial Diffmentioning

confidence: 99%

When urothelial differentiation pathways go wrong: Implications for bladder cancer development and progression

DeGraff

Cates

Mauney

et al. 2013

Urologic Oncology: Seminars and Original Investigations

View full text Add to dashboard Cite

show abstract

“…In the gastrointestinal tract, KGF stimulates both proliferation and differentiation toward goblet cells (8). Other epithelial cell types that KGF has been reported to stimulate include hepatocytes (8), pulmonary type II pneumocytes (20), mammary gland epithelial cells (19), pancreatic ductal epithelial cells (24), and transitional urothelial cells (22 (10,12).…”

Section: Effects Of Kgf In Normal Animalsmentioning

confidence: 99%

Preclinical and Early Clinical Development of Keratinocyte Growth Factor, an Epithelial- Specific Tissue Growth Factor

Danilenko

1999

Toxicol Pathol

Self Cite

View full text Add to dashboard Cite

Keratinocyte growth factor (KGF) is a 28-kDa heparin-binding member of the fibroblast growth factor (FGF) family ( mucositis. Several dose-and time-variable studies were conducted in normal rhesus macaques to determine the lowest dose and shortest duration of rHuKGF administration required to induce oral mucosal proliferation without other significant systemic effects. Numerous studies were also conducted in murine models of chemotherapy-induced mucositis to fine-tune the dosing schedule. These studies showed that 2-3 days of rHuKGF administration were sufficient to induce significant oral mucosal proliferation and to protect against gastrointestinal mucositis when administered prior to the initiation of chemotherapy. The results from these models were used to design a phase I study in normal human volunteers to evaluate the safety of rHuKGF and its ability to induce oral mucosal proliferation. rHuKGF was well tolerated and induced a significant increase in markers of oral mucosal proliferation following 3 days of administration at the highest doses. Phase I/II studies to evaluate the safety and efficacy of rHuKGF in the prevention of chemotherapy-induced mucositis are currently in progress.

show abstract

“…There have been accumulating understandings on the regulation of urothelial proliferation by peptide growth factors including epidermal growth factor (EGF) (Reznikoff et al, 1987), heparin-binding EGF (Freeman et al, 1997), transforming growth factor a and b (de Boer et al, 1996), and keratinocyte growth factor (Yi et al, 1995). In contrast, the role of lipophilic ligands of nuclear receptors in the regulation of urothelial proliferation has been remained almost unclear.…”

mentioning

confidence: 99%

PPARγ ligands suppress proliferation of human urothelial basal cells in vitro

Kawakami

Arai

Hayashi

et al. 2002

Journal Cellular Physiology

View full text Add to dashboard Cite

Expression of peroxisome proliferator-activated receptor (PPAR) gamma in the human urinary tract through embryonic development suggests its possible roles in the development, proliferation, and differentiation of uroepithelium. Little is known, however, about physiological roles of PPARgamma in the urinary tract. We investigated effects of PPARgamma ligands on the proliferation of normal human urothelial cells and stromal cells cultivated from surgical specimens. Active proliferation in vitro as well as high molecular weight cytokeratin expression indicated that cultured urothelial cells possess basal cell phenotype. PPARgamma protein, expressed predominantly in the epithelial layer of the normal human urinary tract in vivo, was abundantly expressed in urothelial cells but barely detectable in stromal cells in vitro. Natural ligand for PPARgamma, 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)), as well as synthetic ones, troglitazone and pioglitazone, suppressed proliferation of the urothelial cells dose-dependently. These effects were PPARgamma specific because clofibrate or PGF(2alpha) did not affect proliferation of urothelial cells. Neither 9-cis retinoic acid or all-trans retinoic acid (ATRA) at 1 microM showed any synergism on the antiproliferative effects of PPARgamma ligands. Urothelial cells treated with PPARgamma ligands showed drastic morphologic changes and cell cycle arrest at G0/G1 phase accompanied with increased mRNA level of a cyclin-dependent kinase inhibitor p21(WAF1/CIP1). Since 15d-PGJ(2) is present in vivo during the resolution phase of inflammation, these results indicated that PPARgamma might be involved in the terminal phase of urothelial re-epithelialization processes.

show abstract

Keratinocyte Growth Factor Causes Proliferation of Urothelium In Vivo

Abstract: Systemic administration of KGF causes rapid and striking proliferation of urothelium.

Cited by 80 publications

References 18 publications

When urothelial differentiation pathways go wrong: Implications for bladder cancer development and progression

When urothelial differentiation pathways go wrong: Implications for bladder cancer development and progression

Preclinical and Early Clinical Development of Keratinocyte Growth Factor, an Epithelial- Specific Tissue Growth Factor

PPARγ ligands suppress proliferation of human urothelial basal cells in vitro

Contact Info

Product

Resources

About