Abstract
Simple SummaryCancer stem cells (CSCs) are an engine of tumor progression and a source of tumor therapy resistance and regrowth after treatment. Modern conventional therapies can eliminate most non-CSCs, while CSCs often survive cancer treatment, leading to tumor relapse and metastases. Prostate cancer (PCa) is a disease that affects 1 in 8 men in their lifetime. Although the 5-year survival rate of patients with localized or regional PCa is close to 100%, it dramatically decreases to 30% for the patients with distant metastases. Thus, targeting CSCs might be a promising approach to overcome tumor resistance and increase the efficiency of the current cancer treatment strategies. A high aldehyde dehydrogenase (ALDH) activity is a widely accepted marker of prostate CSCs. This review discusses the current state of research regarding the role of individual ALDH enzymatic proteins in PCa development and progression, their possible therapeutic targeting, and future development in this field.Cancer stem cells (CSCs) are the only tumor cells possessing self-renewal and differentiation properties, making them an engine of tumor progression and a source of tumor regrowth after treatment. Conventional therapies eliminate most non-CSCs, while CSCs often remain radiation and drug resistant, leading to tumor relapse and metastases. Thus, targeting CSCs might be a powerful tool to overcome tumor resistance and increase the efficiency of current cancer treatment strategies. The identification and isolation of the CSC population based on its high aldehyde dehydrogenase activity (ALDH) is widely accepted for prostate cancer (PCa) and many other solid tumors. In PCa, several ALDH genes contribute to the ALDH activity, which can be measured in the enzymatic assay by converting 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) aminoacetaldehyde (BAAA) into the fluorescent product BODIPY-aminoacetate (BAA). Although each ALDH isoform plays an individual role in PCa biology, their mutual functional interplay also contributes to PCa progression. Thus, ALDH proteins are markers and functional regulators of CSC properties, representing an attractive target for cancer treatment. In this review, we discuss the current state of research regarding the role of individual ALDH isoforms in PCa development and progression, their possible therapeutic targeting, and provide an outlook for the future advances in this field.
Highlights
Prostate cancer (PCa) is a disease that will prognostically affect 1 in 8 men in their lifetime
This study showed that the chemical inhibition of ALDH1A1 by different imidazo[1,2-α]pyridine derivatives led to the decreased proliferation and clonogenicity in a panel of established PCa cell lines and patient-derived primary epithelial cells [50]
Stevenson et al showed that ALDH1A1, ALDH2, and ALDH9A1 proteins are present in lymph node metastasis specimens of breast cancer, pancreatic ductal adenocarcinoma, and prostate cancer, indicating a potential common role of these proteins in the development of lymph node metastases in patients with different tumor entities [163]
Summary
Prostate cancer (PCa) is a disease that will prognostically affect 1 in 8 men in their lifetime. A high activity of aldehyde dehydrogenases (ALDH) measured by ALDEFLUOR assay is one of the most widely described stem cell markers for PCa [11,12]. This review compiles the current state of research regarding the individual ALDH isoform genes and their contribution to PCa development and progression to outline the potential therapy targets and elicit deregulated expression patterns upon malignancy. Cancers 2021, 13, 4703 evaluates the enzymatic production of a fluorescent negatively charged 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY)-aminoacetate (BAA) converted by ALDH enzymes from an uncharged BODIPY-aminoacetaldehyde (BAAA), as shown in Figure 1 [13]. ALDH1A3 proteins in ALDEFLUOR assay and the regulation of cancer stem cells (CSCs) through retinoic acid (RA) signaling. Prostate cancer cells expressing ALDH1A1 and ALDH1A3 convert uncharged fluorescent ALDH substrate BODIPY-aminoacetaldehyde (BAAA) into negatively charged BODIPY-aminoacetate (BAA− ).
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