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Fibroblast growth factors and their receptors in transitional cell carcinoma
Nicholas P Munro1, Margaret A Knowles
1Cancer Research United Kingdom Clinical Centre in Leeds, St James's University Hospital, Leeds, United Kingdom.
Purpose:
The recent identification in transitional cell carcinoma of mutations in a fibroblast growth factor (FGF) receptor, namely FGF receptor-3, has provoked great interest in the potential usefulness of FGF receptors and their ligands as molecular markers and as targets for bladder cancer therapy. We examined these possibilities in light of the published literature.
Materials And Methods:
We reviewed the world literature on FGFs and their receptors from 1966 to January 2002 using PubMed.
Results:
The recent identification in transitional cell carcinoma of a high frequency of mutations in FGF receptor-3 predicted to activate kinase activity of the receptor indicate a likely role as an oncogene in the urothelium. The finding of FGF receptor-3 mutations only rarely in other tumor types to date indicates surprising urothelial specificity that requires tissue specific approaches for evaluation and exploitation. In contrast, FGF receptor-2 expression is down-regulated in bladder tumors, suggesting a possible tumor suppressor role. Information is available on the expression of FGF receptors-1 and 2 in normal bladder and urine, and in bladder tumors. These angiogenic factors represent potential urine markers of bladder neoplasia, although as single markers they lack sufficient sensitivity and specificity. Some interesting insights into the potential role of these factors have come from studies using in vitro model systems. However, there is little information on the numerous other members of this family of growth factors in the bladder and, therefore, much scope for future studies.
Conclusions:
It is clear that the FGFs and their receptors have important roles in the development of transitional cell carcinoma. Undoubtedly it will be a focus for much future research. It can be anticipated that members of these protein families would represent useful clinical markers and potential targets for bladder cancer therapy.
Insights
Fibroblast growth factor (FGF) receptors are implicated in bladder cancer development. Mutations in FGF receptor-3 suggest an oncogenic role, while FGF receptor-2 may act as a tumor suppressor, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Transitional cell carcinoma (TCC) is the most common type of bladder cancer.
- Fibroblast growth factors (FGFs) and their receptors play critical roles in cellular processes, including proliferation, differentiation, and angiogenesis.
- Recent studies have identified mutations in FGF receptors in various cancers, prompting investigation into their role in bladder cancer.
Purpose of the Study:
- To review the literature on the role of FGFs and their receptors in bladder cancer.
- To evaluate the potential of FGF receptors and their ligands as molecular markers for bladder cancer.
- To explore the therapeutic potential of targeting FGF signaling pathways in bladder cancer.
Main Methods:
- A comprehensive literature search was conducted using PubMed, covering publications from 1966 to January 2002.
- The review focused on studies investigating FGFs, their receptors, and their involvement in bladder cancer.
- Data on gene mutations, expression levels, and functional roles were analyzed.
Main Results:
- Mutations in FGF receptor-3 (FGFR3) are frequently found in TCC and are predicted to activate its kinase activity, suggesting an oncogenic role in urothelial cells.
- FGFR3 mutations show remarkable urothelial specificity, indicating potential for tissue-specific therapeutic strategies.
- Down-regulation of FGF receptor-2 (FGFR2) expression in bladder tumors suggests a potential tumor suppressor function.
- FGF receptors-1 and -2 are expressed in normal bladder, urine, and tumors, with angiogenic properties making them potential, though not sufficiently sensitive or specific, urine markers for bladder neoplasia.
- Limited information exists on other FGF family members in the bladder, highlighting avenues for future research.
Conclusions:
- FGFs and their receptors are significantly involved in the pathogenesis of TCC.
- These factors are promising candidates for future research in bladder cancer.
- FGF family members are anticipated to serve as valuable clinical markers and potential therapeutic targets for bladder cancer treatment.