Item Details

title

Effect of SPARC on Macrophage Differentiation: Impact on Bladder Cancer

author

Diab, Mariam

abstract

Bladder cancer is the 4th in new cases and 8th in deaths among American males, and the most common malignancy is urothelial carcinoma. Previous studies in our lab had reported that SPARC exerts a tumor suppressor effect on bladder cancer through distinct differential effects on cancer cells and TAMs. Loss of SPARC has been associated with bladder carcinogenesis, tumor progression, and metastasis, and exhibits an inverse correlation with increased macrophage infiltration during cancer progression. Macrophages can be activated to an M1 pro-inflammatory or M2 anti-inflammatory phenotype closely resembling TAMs. We propose that SPARC plays an inhibitory role on macrophage phenotypic commitment to an M2 pro-tumorigenic phenotype. We first tested the effects of exogenous SPARC on human U937 macrophage cell line differentiation and polarization and found that SPARC exhibited differential effects on macrophage expression, differentiation, and immune suppression markers. We also investigated the effects of endogenous Sparc on the differentiation and polarization of KO and WT BMDMCs. Sparc KO BMDMCs exhibited significantly higher M2 cell surface markers and Il4, Il4r, and Il13r transcripts than WT. We concluded that SPARC plays a tumor suppressor role in the tumor microenvironment and inhibits macrophage commitment to an M2 TAM phenotype.

subject

Bladder Cancer

macrophage differentiation

macrophage polarization

SPARC

Tumor associated macrophages

contributor

Said, Neveen (advisor)

Levi, Nicole (committee member)

Gmeiner, William (committee member)

date

2024-05-23T08:36:27Z (accessioned)

2025-05-22T08:30:07Z (available)

2024 (issued)

degree

Biomedical Science – MS (discipline)

embargo

2025-05-22 (terms)

identifier

http://hdl.handle.net/10339/109460 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis