Caveolin-1 is a modulator of clonogenicity in renal cell carcinoma

Gutteridge, Robert 2015. Caveolin-1 is a modulator of clonogenicity in renal cell carcinoma. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Renal cell carcinoma (RCC) represents a group of aggressive tumours of the kidney. These tumours have a high propensity for metastasis and are extremely treatment refractive after disease relapse. Therefore, the identification of new therapeutic targets is of great importance. One such potential target for therapy are cancer stem cells (CSCs). CSCs are populations of cells imbued with a stem cell-like phenotype capable of driving tumour formation, metastasis and chemoresistance. As such, reliable methods for the identification of CSC populations and defining targets important to their functionality, in hopes of developing more potent therapeutics is of great importance. Previous work has found CAV1 to play a significant role in the malignant progression of RCC and also in the maintenance of adult stem cell populations. As such, this work aimed to understand if common markers of CSC phenotype in combination with CAV1 can act indicators of poor prognostic outcome in clinically confined RCC. Furthermore, this work sought to identify CSC populations from RCC cell lines using a panel of surface markers common to embryonic, mesenchymal and cancer stem cells. Then, understand if CAV1 is responsible for driving the CSC phenotype in these CSC populations by regulating one of the major characteristics of CSC biology, self-renewal. Co-expression of CD44 and CAV1 in RCC tumours indicated greatly reduced disease free survival in clinically confined RCC. Additionally, CD44/CAV1 was found to be the most significant covariate in predicting disease recurrence. In vitro analysis, using a panel of CSC related markers, was unable of identifying a putative CSC population. However, CAV1 expression in the VHL positive CAKI-1 cell line was important for the maintenance of clonogenicity. Incubation of CAV1 deficient CAKI-1 cells under hypoxic conditions was able to restore lost clonogenicity. Further iv work revealed that CAV1 maintains clonogenicity in CAKI-1 through activation of STAT3 and -catenin. This suggests an important role for CAV1 in the maintenance of clonogenicity through STAT3 activation in VHL competent RCC.

Item Type:	Thesis (PhD)
Date Type:	Publication
Status:	Unpublished
Schools:	Pharmacy
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Renal cell carcinoma, Caveolin-1, Cancer stem cell, clonogenicity, STAT3, CD44
Date of First Compliant Deposit:	20 June 2016
Last Modified:	25 Aug 2023 11:25
URI:	https://orca.cardiff.ac.uk/id/eprint/91911

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