Cyclooxygenase inhibitors may be more effective in hormone-dependent endometrial cancers: interaction between cyclooxygenase and aromatase

We read with great interest the article by Toyoki et al. [1Go]. They found a positive association between vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (cox-2) on angiogenesis at an early stage in the growth of uterine endometrial cancer. They suggested that long-term administration of cox-2 inhibitors might be effective in the suppression of recurrent initiation of uterine endometrial cancers after curative resection. Currently, in vivo and in vitro studies on the uterine effects of aromatase inhibitors are limited. It is well known that some endometrial cancers are hormonally dependent. Since most of uterine endometrial cancers are postmenopausal, a principal source of circulating estrogen in these patients is from the conversion of adrenal androstenedione by aromatase. In addition to peripheral aromatization, aromatase is also elevated in endometrial cancer stroma [2Go]. Morales et al. [3Go], in the same issue of Annals of Oncology, also showed that third-generation aromatase inhibitors may prevent endometrial growth and reverse tamoxifen-induced uterine changes in postmenopausal breast cancer patients.

Furthermore, even though there was no direct data about the association between aromatase and cox in uterine endometrial cells, it has been shown that increased secretion of prostaglandins, such as prostaglandin E2 from constitutive cox-1 and inducible cox-2 isozymes present in epithelial and stromal cell compartments, will result in both autocrine and paracrine actions to increase aromatase expression in normal and malignant breast cells [4Go]. In the light of above information, cox-2 inhibitors may be more effective in hormone-dependent uterine endometrial cancers by further suppressing aromatase activity. In vitro and in vivo studies on uterine endometrial cancers are warranted to support our hypothesis.

K. Altundag1,*, O. Altundag, P. Morandi2 and B. Ozcakar3

1 Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 2 Department of Medical Oncology, S. Bortolo General Hospital, Vicenza, Italy; 3 Department of Chest Disease, Fatih University Faculty of Medicine, Ankara, Turkey

(* Email: drkadri{at}usa.net)

References

1. Toyoki H, Fujimoto J, Sato E et al. Clinical implications of expression of cyclooxygenase-2 related to angiogenesis in uterine endometrial cancers. Ann Oncol 2005; 16: 51–55.[Abstract/Free Full Text]

2. Wanatbe K, Sasano H, Harada N et al. Aromatase in human endometrial carcinoma and hyperplasia. Immunohistochemical, in situ hybridization, and biochemical studies. Am J Pathol 1995; 146: 491–500.[Abstract]

3. Morales L, Timmerman D, Neven P et al. Third generation aromatase inhibitors may prevent endometrial growth and reverse tamoxifen-induced uterine changes in postmenopausal breast cancer patients. Ann Oncol 2005; 16: 70–74.[Abstract/Free Full Text]

4. Richards JA, Petrel TA, Brueggemeier RW. Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells. J Steroid Biochem Mol Biol 2002; 80: 203–212.[CrossRef][ISI][Medline]





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