The role of liver microenvironment in hepatic metastasis
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REVIEW
The role of liver microenvironment in hepatic metastasis Tovah Williamson1, Nikhila Sultanpuram1 and Hossein Sendi1,2*
Abstract Metastasis is still poorly understood and thus further research must be conducted to provide insight into the driving factors. Novel research has revealed the significance of the microenvironment in the delegation of metastasis, expanding the field of cancer metastasis to cells and cell environments surrounding the migrated tumor cells. Research on hepatic metastasis is an ever-growing domain of this field, as several primary tumors can metastasize to the liver. The two features within the liver that promote metastasis—cellular and acellular—are found in the current interpretation of liver microenvironment. Novel findings of both are included in this review. Different hypotheses detailing the methods by which metastasis can occur must be included to understand the significance of the microenvironment, as well as a brief overview of the methods that can be used during research. This review aims to highlight the importance of liver microenvironment on the development or potential regression of hepatic metastasis through discussing both acellular and cellular components of liver microenvironment and their interaction with metastasis. Keywords: Cancer, Tumor, CTC, ECM, Metastatic Introduction Organ microenvironments are an undeniable component for metastasis, enabling proliferation of cancer cells to organ systems external to the primary tumor. Migration of cancer cells requires compatibility with the destination, particularly with the microenvironment. Hepatic metastases can arise from the primary cancers in different locations within the human body. Both the acellularsuch as extracellular matrix (ECM) proteins (i.e. collagen) and the cellular components of the liver such as Kupffer cells (KCs), hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs) contribute to the metastatic ability of tumors of different origins. Common incidences of liver metastasis occur in colorectal cancers, as these cells can take advantage of both the proximity (as a great amount of venous drainage is to the liver) and highly vascular nature of the liver [1]. A statistical analysis revealed that of 4399 patients with cancer, 41% *Correspondence: [email protected] 1 Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC, USA Full list of author information is available at the end of the article
of them experienced metastasis to the liver, marking it as the second greatest metastatic site, just behind nonspecific lymph node metastases [2]. The ECM is the major acellular component contributing to the liver microenvironment, and consequently the microenvironment of the tumor. The matrix of biological tissue serves as a framework by which cells organize, intertwined with the local vasculature. The ECM also contains domains that allow proteins to bind, which are important for cell–cell communication as well as specific function. ECM proteins can interac
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