Abstract
Tumor stroma forms a distinct microenvironment that critically regulates the development and behavior of malignant neoplasms, including hepatobiliary cancers. The formation of stroma is a complex process and a decisive pathogenic mechanism for cancer growth, differentiation, invasion, and metastatic spread. Hepatic neoplasms show striking coevolution of cancerous cells and their associated stromal microenvironment, including components of the extracellular matrix. Tumor stroma provides the proliferating cancer cell population with nutrients, oxygen, and growth factors that are stored in this microenvironment. Stroma is also the cell system that initiates and regulates tumor angiogenesis. The cell systems that mediate all these complex functions include mesenchymal stem cells as a major source of stromal spindle cells, hepatic stellate cells, cancer-associated fibroblasts, myofibroblasts, endothelial cells and their progenitors, and a large number of various leukocytes. Mesenchymal stem cells as a source of stromal cells and cells of premetastatic niches in part originate from extrahepatic sites, mainly blood and bone marrow. Stromal leukocytes provide a distinct inflammatory microenvironment for cancer that mediates growth control and provides chemokines and cytokines involved in invasion and spread. Inflammatory stromal cells comprise tumor-associated macrophages, lymphocytes, myeloid suppressor cells, and granulocytes.
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Zimmermann, A. (2016). Tumor Stroma, Desmoplasia, and Stromagenesis. In: Tumors and Tumor-Like Lesions of the Hepatobiliary Tract. Springer, Cham. https://doi.org/10.1007/978-3-319-26587-2_185-1
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