A quartet of cancer stem cell niches in hepatocellular carcinoma

• Published in: Cytokine & growth factor reviews 2024-10, Vol.79, p.39-51
• Main Authors: Balaji, Neha, Kukal, Samiksha, Bhat, Anjali, Pradhan, Nikita, Minocha, Shilpi, Kumar, Saran
• Format: Article
• Language: English
• Subjects: Cancer stem cell niche; Hepatic cancer stem cell; Hepatocellular carcinoma; Therapy resistance; Tumor microenvironment; Tumor recurrence
• ISSN: 1359-6101
• DOI: 10.1016/j.cytogfr.2024.08.007

Hepatocellular Carcinoma (HCC), the most prevalent type of primary liver cancer, is known for its aggressive behavior and poor prognosis. The Cancer Stem Cell theory, which postulates the presence of a small population of self-renewing cells called Cancer Stem Cells (CSCs), provides insights into various clinical and molecular features of HCC such as tumor heterogeneity, metabolic adaptability, therapy resistance, and recurrence. These CSCs are nurtured in the tumor microenvironment (TME), where a mix of internal and external factors creates a tumor-supportive niche that is continuously evolving both spatially and temporally, thus enhancing the tumor's complexity. This review details the origins of hepatic CSCs (HCSCs) and the factors influencing their stem-like qualities. It highlights the reciprocal crosstalk between HCSCs and the TME (hypoxic, vascular, invasive, and immune niches), exploring the signaling pathways involved and how these interactions control the malignant traits of CSCs. Additionally, it discusses potential therapeutic approaches targeting the HCSC niche and their possible uses in clinical practice. [Display omitted] •HCSCs are critical drivers of HCC malignancy, and response to therapy.•The review underscores the reciprocal interactions between HCSCs and various TME niches.•HCSCs exhibit plasticity and multiple mechanisms of therapy resistance.•HCSCs thrive in a dynamic tumor microenvironment that fosters a supportive niche.