New Perspectives on Sex Steroid Hormones Signaling in Cancer-Associated Fibroblasts of Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Smoking is a major risk factor for NSCLC; however, the incidence of NSCLC among nonsmokers, especially women, is increasing. Therefore, sex hormones are associated with NSCLC progression and their significance has been demonstrated. Cancer-associated fibroblasts, which reside in cancer stroma, are important components that significantly influence cancer progression by interacting with other cells, including cancer cells. We focused on the roles of cancer-associated fibroblasts in hormonal cell–cell interactions in NSCLC and their prospects. ABSTRACT: The importance of sex hormones, especially estrogen, in the pathogenesis of non-small-cell lung cancer (NSCLC) has attracted attention due to its high incidence among young adults and nonsmokers, especially those who are female. Cancer-associated fibroblasts (CAFs) reside in the cancer stroma and influence cancer growth, invasion, metastasis, and acquisition of drug resistance through interactions with cancer cells and other microenvironmental components. Hormone-mediated cell–cell interactions are classic cell–cell interactions and well-known phenomena in breast cancer and prostate cancer CAFs. In cancers of other organs, including NSCLC, the effects of CAFs on hormone-receptor expression and hormone production in cancer tissues have been reported; however, there are few such studies. Many more studies have been performed on breast and prostate cancers. Recent advances in technology, particularly single-cell analysis techniques, have led to significant advances in the classification and function of CAFs. However, the importance of sex hormones in cell–cell interactions of CAFs in NSCLC remains unclear. This review summarizes reports on CAFs in NSCLC and sex hormones in cancer and immune cells surrounding CAFs. Furthermore, we discuss the prospects of sex-hormone research involving CAFs in NSCLC.