Abstract
Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl leukotriene (CysLT) pathway is involved in several signal pathways, having various functions in different tissues. We summarized major findings of studies about the roles of the CysLT pathway in cancer. Many in vitro studies suggested the roles of CysLTs in cell survival/proliferation via CysLT1 receptor (CysLT1R). CysLT1R antagonism decreased cell vitality and induced cell death in several types of cancer cells, such as colorectal, urological, breast, lung and neurological malignancies. CysLTs were also associated with multidrug resistance of cancer, and CysLT1R antagonism might reverse chemoresistance. Some animal studies demonstrated the beneficial effects of CysLT1R antagonist in inhibiting tumorigenesis and progression of some cancer types, particularly colorectal cancer and lung cancer. The expression of CysLT1R was shown in various cancer tissues, particularly colorectal cancer and urological malignancies, and higher expression was associated with a poorer prognosis. The chemo-preventive effects of CysLT1R antagonists were demonstrated in two large retrospective cohort studies. In summary, the roles of the CysLT pathway in cancer have been delineated, whereas further studies are still warranted.
Highlights
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The tumor microenvironment is composed of the extracellular matrix and basement membrane, endothelial cells, cancer-associated fibroblasts, neuroendocrine cells, adipose cells, pericytes and tumor-infiltrating immune cells [4]
CysLT1 receptor (CysLT1R) expression was demonstrated in human primary mediastinal B-cell lymphoma cell lines (Med-B1, Karpas-1106P); cysteinyl leukotriene (CysLT) induced a calcium signal in Med-B1 cells, which could be blocked by zafirlukast [42]
Summary
Cancer is a major public health issue/concern worldwide and is the leading cause of death in many countries, including Taiwan [1,2]. Many types of procedures and medications are available for cancer treatment, including surgery, radiotherapy, chemotherapeutic agents and targeted therapy. A tumor and its microenvironment interact constantly and influence each other Such interactions begin at the very early phase. Such interactions begin at the very early phase of tumor formation, and continue during primary growth, local invasi2oonf ,26intravasation and establishment at the metastatic site. LTB4 could trigger aggregation and adherence of leukocytes to the endothelium. LTB4 is involved in many inflammatory diseases, including dermatitis, arthritis, nephritis and chronic obstructive pulmonary disease [10]
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