Unique Roles of Sphingolipids in Selected Malignant and Nonmalignant Lesions of Female Reproductive System

Abstract

Cancer develops as a result of the loss of self-control mechanisms by a cell; it gains the ability to induce angiogenesis, becomes immortal and resistant to cell death, stops responding to growth suppressor signals, and becomes capable of invasion and metastasis. Sphingolipids-a family of membrane lipids-are known to play important roles in the regulation of cell proliferation, the response to chemotherapeutic agents, and/or prevention of cancer. Despite the underlying functions of sphingolipids in cancer biology, their metabolism in different malignant tumors is poorly investigated. Some studies showed marked differences in ceramide content between the tumor and the respective healthy tissue. Interestingly, the level of this sphingolipid could be either low or elevated, suggesting that the alterations in ceramide metabolism in cancer tissue may depend on the biology of the tumor. These processes are indeed related to the type of cancer, its stage, and histology status. In this paper we present the unique roles of bioactive sphingolipid derivative in selected gynecologic malignant and nonmalignant lesions.

Figure 1

Metabolism of sphingolipids: serine palmitoyl transferase (SPT), (dihydro)ceramide synthase(CERS), dihydroceramide desaturase (DES), diacylglycerol (DAG), sphingomyelinases (SMase), SM synthase (SMS), glucosylceramide (GlcCER), glucosylceramide synthase (GCS), ceramide-1-phosphate (Cer-1-P), ceramide kinase (CK), ceramidases (CDases), sphingosine kinase (SK), cerebrosidase (CRS), and phosphatases of CER-1-P and S1P (C1PP and S1PP).

Figure 2

The biological mechanism of sphingolipids involved in the regulation of cancer growth and therapy: ceramide-activated protein phosphatases (CAPP) and diacylglycerol (DAG).