Ovarian Epithelial-Stromal Interactions: Role of Interleukins 1 and 6

Abstract

Ovarian epithelial cancer is the most lethal gynecologic malignancy. The high mortality is attributed to the fact that most cases typically present in late stage when ovarian cancer (OC) has already spread beyond the ovary. Ovarian epithelial cancer cells are shed into intraperitoneal ascites and easily disseminate throughout the peritoneal cavity with preferential metastasis to the omentum, peritoneum, and local organs. Understanding how ovarian epithelial cells interact with and modulate their microenvironment can provide insight into the molecular mechanism(s) involved with malignant transformation and progression which may eventually identify novel diagnostic, prognostic, and therapeutic targets. The objective of this paper is to provide a brief consideration of ovarian surface epithelial-stromal interactions in regard to normal physiological function and tumor progression as influenced by two potentially key interleukins, interleukins-1 (IL-1) and -6 (IL-6), present in the microenvironment. Lastly, we will consider the clinical implications of IL-1 and IL-6 for OC patients.

Minocycline Suppresses Interleukine-6, Its Receptor System and Signaling Pathways and Impairs Migration, Invasion and Adhesion Capacity of Ovarian Cancer Cells: In Vitro and In Vivo Studies

“…It has been shown that both normal and malignant epithelial ovarian cells along with activated immune cells in the stroma produce IL-1β. Moreover, constitutive production of IL-1β by ovarian carcinoma cells stimulates production of cytokines such as IL-6 [34]. To simulate what happens in ovarian tumors, we used IL-1β (10 ng/ml) to induce IL-6 expression in ovarian cancer cells and then examined whether minocycline can block the surge in IL-6 expression.…”

Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research

“…In animal models, the expression of IL-8 is associated with increased tumorigenicity and ascites formation 71,72 . IL-6 has been shown to promote growth 70 , chemoresistance, tumour invasion 73 and angiogenesis 74,75 . High levels of IL-6 (REFS 69,76,77) and IL-10 (REF.…”

Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions

“…It is known that the levels of these cytokines are substantially higher within the peritoneal fluid than in serum 2. Both ILs, as well as their receptors, are expressed at different levels within the epithelial cells of ovarian cancer of various malignancy grades 16,21,22. The tumor-promoting effect of these cytokines involves enhancement of anchorage-independent growth, proliferation, and angiogenesis as well as cellular adhesion and invasion 17,23.…”

“…IL-6 and IL-8 have long been identified as cytokines involved in the neoplastic process leading to the development of ovarian cancer. 21 Because this analysis focused on the levels of cytokines and growth factors within the peritoneal fluid of ovarian cancer patients, it included typical representatives of this class. It is known that the levels of these cytokines are substantially higher within the peritoneal fluid than in serum.…”