Graduation Date

Spring 5-4-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Cancer Research

First Advisor

Grinu Mathew, Ph.D.

Second Advisor

Heather Jensen-Smith, Ph.D.

Third Advisor

Jennifer Black, Ph.D.

Fourth Advisor

Keith Johnson, Ph.D.

Abstract

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental factors in disease progression and treatment outcomes. Intricate molecular mechanisms and genetic variations can be gateways to further understand PC metastasis development. The aim of this thesis is to evaluate how the loss of Axlin Pten/Trp53NULL cells promote a metastatic phenotype with a potential role in metastatic adaptation. To explore this hypothesis, we generated a PC lung metastasis model with Axl knockout (KO; CRISPR) in Pten/Trp53NULLRapidCaP-derived cell lines. These in-vivo trials provided insights into the biological disparities between KO and WT cell lines using transcriptomics, immunohistochemistry, and multiphoton-photon microscopy-based collagen imaging. By assessing the metastatic capacity of parental and knockout cell lines in vivo we demonstrated faster incidence of overt metastases in the AxlNULL model, underscoring the significance of AXL loss in driving PC metastasis.

Comments

2024 Copyright, the authors

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