Journal of Clinical and Molecular Endocrinology

Letter to Editor

Lung cancer remains the leading cause of cancer death in men and has increased worldwide in women in the last decades [1]. Lung cancer behavior appears to be different between women and men [2]. However information about these differences is still controversial maybe because several studies compare pathological characteristics by sex but not by hormonal status. When premenopausal women have been considered in some studies, they coursed with more advanced stages of cancer at diagnosis, poorly differentiated tumors and worse prognosis compared to postmenopausal women and men [3]. Some studies have showed that sex hormones, mainly estradiol, through its receptor ERβ have an important role in lung carcinogenesis [4,5]. Previously we reported that lung adenocarcinomas from premenopausal women exhibited higher signal of estrogen receptor (ERβ), as well as CXCL₁₂ and CXCR₄ compared to adenocarcinomas from postmenopausal women and men, suggesting that expression of this proteins in tumors could be related with estradiol levels [6]. Recently we also reported that estradiol stimulates CXCR₄ expression in a doseand a time-dependent manner and favors CXCL₁₂/CXCR₄ activation pathway by promoting lung cancer cell migration in vitro. In the same study, Tamoxifen treatment reduced CXCR₄ expression and suppressed lung cancer cell migration [7]. The CXCL₁₂/CXCR₄ pathway is an important Chemokine/Receptor axis, involved in proliferation, migration and metastasis in lung cancer. Expression of CXCR₄ is related with advanced stages, metastasis and poor survival in patients with lung cancer. High expression of CXCR₄ in lung adenocarcinoma from premenopausal women explains partially the worst prognosis of these patients. Estradiol promotes lung carcinogenesis in several forms; we found other mechanism by which this hormone might stimulate lung cancer progression. Due to the role of estrogen in lung cancer and the effect that antiestrogen drugs have on lung cancer cells, E2/ER pathway can be seen a new therapeutic target. Although further research is needed on the role of estrogen in lung cancer, it seems to identify Estrogen receptor (ERβ) and aromatase enzyme expression in lung tumours, might be important in designing new therapeutic strategies in lung cancer based in antiestrogen drugs, since by inhibiting estrogenic pathway, other important signalling pathways involved in lung carcinogenesis are also affected.

References

1. Youlden DR, Cramb SM, Baade PD (2008). The International Epidemiology of Lung Cancer: geographical distribution and secular trends. Journal of thoracic oncology: Official publication of the International Association for the Study of Lung Cancer 3: 819-831
2. Powell HA, Iyen-Omofoman B, Hubbard RB, Baldwin DR, Tata LJ (2013) The association between smoking quantity and lung cancer in men and women. Chest 143: 123-129.
3. Albain KS, Unger JM, Gotay CC, Davies M, Edelman M, et al. (2007). Toxicity and survival by sex in patients with advance non-small cell lung carcinoma on modern Southwest Oncology Group (SWOG) trials. In 2007 Anual Meeting Proceedings, ed. ASoC Oncology, p. 7549: American Society of Clinical Oncology
4. Niikawa H, Suzuki T, Miki Y, Suzuki S, Nagasaki S, et al. (2008). Intratumoral estrogens and estrogen receptors in human non-small cell lung carcinoma. Clinical cancer research : An official journal of the American Association for Cancer Research 14: 4417-4426
5. Stabile LP1, Dacic S, Land SR, Lenzner DE, Dhir R, et al. (2011) Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome. Clin Cancer Res 17: 154-164.
6. Rodriguez-Lara V, Pena-Mirabal E, Baez-Saldana R, Esparza-Silva AL, Garcia-Zepeda E, et al. 2014. Estrogen receptor beta and CXCR4/CXCL12 expression: Differences by sex and hormonal status in lung adenocarcinoma. Arch Med Res 45: 158-169.
7. Rodriguez-Lara V, Ignacio GS, Cerbón Cervantes MA (2017) Estrogen induces CXCR4 overexpression and CXCR4/CXL12 pathway activation in lung adenocarcinoma cells in vitro. Endocr Res.