Ovarian cancer (OC) most frequently arises from the ovarian surface epithelium (OSE), which comprises a single layer of mesothelial, squamous-to-cuboidal cells covering the entire surface of the ovary (1). This dynamic cellular layer and underlying basement membrane is breached and repaired each time a follicle ovulates, which can happen up to around 400 times in an average woman’s lifetime. It is, therefore, perhaps not surprising that there is a positive association between ovulation and OC and that a majority of OCs arise from the OSE. OC has genetic and environmental aetiologies, and there is growing evidence for inflammatory involvement as well. Ovulation is a natural inflammatory process, the suppression of which by pregnancy, breast-feeding, or oral contraception reduces OC risk. On the other hand, environmental factors and medical conditions associated with ovarian inflammation such as use of talc, endometriosis, ovarian cysts, and hyperthyroidism increase OC risk (2). If inflammation promotes cancer (3,4), we argue that antiinflammation is quite likely to be protective. In this chapter, we rehearse evidence that inflammation is integral to ovulation and consider how associated antiinflammatory mechanisms might impact OC initiation and progression.
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References
Auersperg N, Wong AS, Choi KC, et al. (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22:255–88.
Ness RB, Cottreau C (1999) Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 91:1459–67.
Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7:211–17.
Fleming JS, Beaugie CR, Haviv I, et al. (2006) Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol Cell Endocrinol 247:4–21.
Espey LL (1994) Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod 50:233–8.
Richards JS, Russell DL, Ochsner S, et al. (2002) Ovulation: new dimensions and new regulators of the inflammatory-like response. Annu Rev Physiol 64:69–92.
Murdoch WJ, Wilken C, Young DA (1999) Sequence of apoptosis and inflammatory necrosis within the formative ovulatory site of sheep follicles. J Reprod Fertil 117:325–9.
Rae MT, Hillier SG (2005) Steroid signalling in the ovarian surface epithelium. Trends Endocrinol Metab 16:327–33.
Murdoch WJ (1995) Programmed cell death in preovulatory ovine follicles. Biol Reprod 53:8–12.
Ghahremani M, Foghi A, Dorrington JH (1999) Etiology of ovarian cancer: a proposed mechanism. Med Hypotheses 52:23–6.
Kirsner RS, Eaglstein WH (1993) The wound healing process. Dermatol Clin 11:629–40.
Verrecchia F, Mauviel A (2004) TGF-beta and TNF-alpha: antagonistic cytokines controlling type I collagen gene expression. Cell Signal 16:873–80.
Yang WL, Godwin AK, Xu XX (2004) Tumor necrosis factor-alpha-induced matrix proteolytic enzyme production and basement membrane remodeling by human ovarian surface epithelial cells: molecular basis linking ovulation and cancer risk. Cancer Res 64:1534–40.
Rae MT, Niven D, Ross A et al. (2004) Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by microarray analysis. J Endocrinol 183:19–28.
Kagan HM, Li W (2003) Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem 88:660–72.
Erler JT, Bennewith KL, Nicolau M, et al. (2006) Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440:1222–6.
Bukulmez O, Arici A (2000) Leukocytes in ovarian function. Hum Reprod Update 6:1–15.
Ness RB, Cottreau C (1999) Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 91:1459–673.
Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441:431–6.
Coussens LM, Tinkle CL, Hanahan D, et al. (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 1:481–90.
Tiano HF, Loftin CD, Akunda J, et al. (2002) Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res 62:3395–401.
Aggarwal BB, Shishodia S, Sandur SK, et al. (2006) Inflammation and cancer: How hot is the link? Biochem Pharmacol 72:1605–21.
Grosch S, Maier TJ, Schiffmann S, Geisslinger G, et al. (2006) Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst 98:736–47.
Tomlinson JW, Walker EA, Bujalska IJ, et al. (2004) 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 25:831–66.
Tetsuka M, Thomas FJ, Thomas MJ, et al. (1997) Differential expression of messenger ribonucleic acids encoding 11beta-hydroxysteroid dehydrogenase types 1 and 2 in human granulosa cells. J Clin Endocrinol Metab 82:2006–9.
Yong PY, Thong KJ, Andrew R, et al. (2000) Development-related increase in cortisol biosynthesis by human granulosa cells. J Clin Endocrinol Metab 85:728–33.
Tetsuka M, Haines LC, Milne M, et al. (1999) Regulation of 11beta-hydroxysteroid dehydrogenase type 1 gene expression by LH and interleukin 1beta in cultured rat granulosa cells. J Endocrinol 163:417–23.
Yong PY, Harlow C, Thong KJ, et al. (2002) Regulation of 11beta-hydroxysteroid dehydrogenase type 1 gene expression in human ovarian surface epithelial cells by interleukin-1. Hum Reprod 1:2300–6. Erratum in: Hum Reprod 17:3009.
Rae MT, Niven D, Critchley HO, et al. (2004) Antiinflammatory steroid action in human ovarian surface epithelial cells. J Clin Endocrinol Metab 89:4538–44.
Fleming JS, Beaugie CR, Haviv I, et al. (2006) Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol Cell Endocrinol 247:4–21.
Langdon SP, Lawrie SS, Hay FG, et al. (1988) Characterization and properties of nine human ovarian adenocarcinoma cell lines. Cancer Res 48:6166–72.
Rabbitt EH, Gittoes NJ, Stewart PM, et al. (2003) 11beta-hydroxysteroid dehydrogenases, cell proliferation and malignancy. J Steroid Biochem Mol Biol 85:415–21.
Gubbay O, Guo W, Rae MT, et al. (2005) Inflammation-associated gene expression is altered between normal human ovarian surface epithelial cells and cell lines derived from ovarian adenocarcinomas. Br J Cancer 92:1927–33.
Altinoz MA, Korkmaz R (2004) NF-kappaB, macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer. Neoplasma 51:239–47.
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Hillier, S.G., Rae, M.T., Gubbay, O. (2008). Ovulation and Ovarian Cancer. In: Li, J.J., Li, S.A., Mohla, S., Rochefort, H., Maudelonde, T. (eds) Hormonal Carcinogenesis V. Advances in Experimental Medicine and Biology, vol 617. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69080-3_16
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