New insights into the functions of Cox-2 in skin and esophageal malignancies

Abstract

Understanding the cellular and molecular mechanisms of tumor initiation and progression for each cancer type is central to making improvements in both prevention and therapy. Identifying the cancer cells of origin and the necessary and sufficient mechanisms of transformation and progression provide opportunities for improved specific clinical interventions. In the last few decades, advanced genetic manipulation techniques have facilitated rapid progress in defining the etiologies of cancers and their cells of origin. Recent studies driven by various groups have provided experimental evidence indicating the cellular origins for each type of skin and esophageal cancer and have identified underlying mechanisms that stem/progenitor cells use to initiate tumor development. Specifically, cyclooxygenase-2 (Cox-2) is associated with tumor initiation and progression in many cancer types. Recent studies provide data demonstrating the roles of Cox-2 in skin and esophageal malignancies, especially in squamous cell carcinomas (SCCs) occurring in both sites. Here, we review experimental evidence aiming to define the origins of skin and esophageal cancers and discuss how Cox-2 contributes to tumorigenesis and differentiation.

Preparation, COX-2 Inhibition and Anticancer Activity of Sclerotiorin Derivatives

“…COX-2 is known as an important enzyme in the inflammation process that has tumorigenesis function, and can promote cancer cells proliferation, migration and invasion [ 11 , 12 ]. Zoological and epidemiological studies have shown that COX-2 is closely associated with malignant tumors in recent years [ 13 , 14 , 15 ]. COX-2 over expression has been detected in lung cancer, colon cancer, stomach cancer, breast cancer and other tumors [ 16 , 17 , 18 ].…”

Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review)

“…COX-2 is released by macrophage type II cells, cancer-associated fibroblasts and tumor cells to the cancer microenvironment ( 16 ). In a healthy state, COX-2 is involved in the maintenance of cellular homeostasis; however, when homeostasis is perturbed by certain diseases, it may respond to homeostatic dysregulation and lead to the development of cancer ( 17 ). Several factors affect COX-2 expression ( 18 ), and its overexpression may be explained by the mechanisms of transcriptional and/or post-transcriptional regulation ( 19 ).…”

“…However, COX-2 knockdown significantly suppresses the degree of differentiation in genetically modified mice bearing cutaneous cancer ( 46 ) and esophageal cancer ( 47 ). Notably, the lack of differentiation is an important hallmark of cancer cells ( 17 ). A recent study demonstrated that COX-2 can initiate the formation of aggressive cancer cells from tumor-prone stem cells in mouse skin, and is involved in the occurrence and progression of epithelial cancer cells ( 17 ).…”

“…Notably, the lack of differentiation is an important hallmark of cancer cells ( 17 ). A recent study demonstrated that COX-2 can initiate the formation of aggressive cancer cells from tumor-prone stem cells in mouse skin, and is involved in the occurrence and progression of epithelial cancer cells ( 17 ).…”

The landscape of GPCR signaling in the regulation of epidermal stem cell fate and skin homeostasis

“…Instead, eicosanoids have more profound effects in skin inflammatory diseases and carcinogenesis‐induced skin tumor progression, where they promote keratinocyte proliferation and malignant transformation. Prostaglandins, particularly prostaglandin E2 (PGE2), are the most studied for their effects in skin carcinogenesis and for being the target of nonsteroidal anti‐inflammatory drugs (NSAIDs) (reviewed in References 65, 66). Keratinocytes express the prostaglandin synthases COX1 and 2 ( PTGS1/2 ) and PGE2 receptors (EP or PTGER1‐4 ).…”