The Roles of Fibroblast Growth Factors in the Testicular Development and Tumor

Fibroblast growth factors (FGFs) are classically known as hormonal factors and recent studies have revealed that FGFs have a key role in regulating growth and development of several reproductive organs, including the testis. The testis is mainly consisted of germ cells, Sertoli cells and Leydig cells to develop and maintain the male phenotype and reproduction. This review summarizes the structure and fuctions of testis, the roles of FGFs on testicular development and potential involvement in testicular tumor and its regulatory mechanism. Among 23 members of FGFs, the FGF-1, FGF-2, FGF-4, FGF-8, FGF-9, and FGF-21 were involved and describe in details. Understanding the roles and mechanism of FGFs is the foundation to modeling testicular development and treatments in testicular disease. Therefore, in the last part, the potential therapy with FGFs for the testis of cancer and diabetes was also discussed.

Download Full-text

Discrete cell- and stage-specific localisation of fibroblast growth factors and receptor expression during testis development

Journal of Endocrinology ◽

10.1677/joe.0.1640149 ◽

2000 ◽

Vol 164 (2) ◽

pp. 149-159 ◽

Cited By ~ 36

Author(s):

B Cancilla ◽

A Davies ◽

M Ford-Perriss ◽

GP Risbridger

Keyword(s):

Growth Factors ◽

Expression Profiles ◽

Fibroblast Growth Factors ◽

Receptor Expression ◽

Adjacent Cell ◽

Testicular Development ◽

Fibroblast Growth ◽

Testis Development ◽

Functional Variants ◽

Alternative Mrna Splicing

Fibroblast growth factors (FGFs) are a family of heparin binding proteins involved in many biological processes. These growth factors act through tyrosine kinase receptors (FGFRs); we have previously used immunohistochemistry to study FGFRs-1-4 in foetal, immature and adult rat testes, and found a discrete cell- and stage-specific localisation. Alternative mRNA splicing of FGFRs-1-3 leads to functional variants (IIIb and IIIc) with distinct ligand binding affinities, therefore we have identified the specific expression of functional FGFR variants and the expression and localisation of FGF ligands in testes from foetal, immature and adult rats. Using reverse transcriptase-polymerase chain reaction (RT-PCR), we found that mRNAs for FGFR-1 IIIb and IIIc, FGFR-2 IIIc, FGFR-3 IIIc and FGFR-4 were expressed in foetal, immature and adult testes. Ligands FGFs-1-5, and -8, which can signal through these receptors, were also expressed in testes at each age. Localisation of the ligands FGFs-1, -3 and -4 to rat testes by immunohistochemistry showed a discrete cell- and stage-specific localisation that altered during testis development. This study has shown that the ligands FGFs-1, -3 and -4 are expressed in the testis and have the capacity to signal through appropriate receptors that are also co-localised or expressed in adjacent cell types in the testis. Collectively, the expression profiles of the seven FGFR variants and FGFs-1-5 and -8 suggest a functional importance in testicular development and spermatogenesis. It is concluded that, future studies on the role of other FGF ligands, in particular FGFs-1-4, are warranted.

Download Full-text

Faculty Opinions recommendation of Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1022729.260670 ◽

2004 ◽

Author(s):

Harukazu Nakamura

Keyword(s):

Growth Factors ◽

Fibroblast Growth Factors ◽

Fibroblast Growth

Download Full-text

Faculty of 1000 evaluation for Effects of Chenodeoxycholic Acid on the Secretion of Gut Peptides and Fibroblast Growth Factors in Healthy Humans.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.718021349.793480872 ◽

2013 ◽

Author(s):

Ian Beales

Keyword(s):

Growth Factors ◽

Chenodeoxycholic Acid ◽

Fibroblast Growth Factors ◽

Fibroblast Growth ◽

Gut Peptides ◽

Healthy Humans

Download Full-text

Cytogenetics, Immunostaining for Fibroblast Growth Factors, p53 Sequencing, and Clinical Features of Two Cases of Cystosarcoma Phyllodes

Molecular Diagnosis ◽

10.2165/00066982-200005030-00003 ◽

2000 ◽

Vol 5 (3) ◽

pp. 179-190 ◽

Cited By ~ 9

Author(s):

PAUL V. WOOLLEY ◽

SUSANNE M. GOLLIN ◽

WAHEEB RISKALLA ◽

SYDNEY FINKELSTEIN ◽

DAVID F. STEFANIK ◽

...

Keyword(s):

Growth Factors ◽

Clinical Features ◽

Fibroblast Growth Factors ◽

Fibroblast Growth ◽

Cystosarcoma Phyllodes

Download Full-text

Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications

Current Drug Targets ◽

10.2174/1389450120666190112145409 ◽

2019 ◽

Vol 20 (8) ◽

pp. 852-870

Author(s):

Hassan Dianat-Moghadam ◽

Ladan Teimoori-Toolabi

Keyword(s):

Growth Factors ◽

Wound Repair ◽

Fibroblast Growth Factors ◽

Predictive Biomarkers ◽

Fibroblast Growth ◽

Loss Of Function ◽

Cellular Processes ◽

Fgfr Signaling ◽

Proliferation And Metastasis ◽

Immense Potential

Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations, and changes in tumor–stromal cells interactions, is associated with the development and progression of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms in human disease and tumor progression leading to the presentation of emerging therapeutic approaches, resistance to FGFR targeting, and clinical potentials of individual FGF family in several human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides several attempts to develop predictive biomarkers and combination therapies for different cancers have been explored.

Download Full-text