HDC and cancer: Notably, most malignant cell lines and experimental tumors highly express L-histidine decarboxylase (HDC), a type of histamine synthase, and contain high concentrations of endogenous histamine, which can collectively regulate a variety of biological responses related to tumor growth through paracrine or autocrine signaling into the extracellular medium (36), as well as angiogenesis, cell invasion, migration, differentiation, apoptosis, death, and the immune response, indicating that histamine may be considered a key mediator in the development and progression of cancer.