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Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Incidence of liver cancer has been increasing in recent years, and the 5-year survival is

Increased lymphangiogenesis and lymph node metastasis, the important prognostic indicators of aggressive hepatobiliary malignancies such as hepatocellular cancer and cholangiocarcinoma, are associated with poor patient outcome. The liver produces 25% to 50% of total lymphatic fluid in the body and has a dense network of lymphatic vessels. The lymphatic system plays critical roles in fluid homeostasis and inflammation and immune response. Yet, lymphatic vessel alterations and function are grossly understudied in the context of liver pathology. Expansion of the lymphatic network has been documented in clinical samples of liver cancer; and although largely overlooked in the liver, tumor-induced lymphangiogenesis is an important player, increasing tumor metastasis in several cancers. This review aims to provide a detailed perspective on the current knowledge of alterations in the hepatic lymphatic system during liver malignancies, as well as various molecular signaling mechanisms and growth factors that may provide future targets for therapeutic intervention. In addition, the review also addresses current mechanisms and bottlenecks for effective therapeutic targeting of tumor-associated lymphangiogenesis.

Cholangiocarcinoma (CCA) is the second most common primary liver tumor and is associated with late diagnosis, limited treatment options, and a 5-year survival rate of around 30%. CCA cell lines were first established in 1971, and since then, only 70 to 80 CCA cell lines have been established. These cell lines have been essential in basic and translational research to understand and identify novel mechanistic pathways, biomarkers, and disease-specific genes. Each CCA cell line has unique characteristics, reflecting a specific genotype, sex-related properties, and patient-related signatures, making them scientifically and commercially valuable. CCA cell lines are crucial in the use of novel technologies, such as three-dimensional organoid models, which help to model the tumor microenvironment and cell-to-cell crosstalk between tumor-neighboring cells. This review highlights crucial information on CCA cell lines, including: i) type of CCA (eg, intra- or extrahepatic), ii) isolation source (eg, primary tumor or xenograft), iii) chemical digestion method (eg, trypsin or collagenase), iv) cell-sorting method (colony isolation or removal of fibroblasts), v) maintenance-medium choice (eg, RPMI or Dulbecco's modified Eagle's medium), vi) cell morphology (eg, spindle or polygonal shape), and vii) doubling time of cells.