Adipokines – Toward the Molecular Dissection of Interactions Between Stromal Adipocytes and Breast Cancer Cells

After more than a half century of efforts, cancer remains the leading cause of death globally, second only to cardiovascular diseases. The World Health Organization estimates that 84 million people will die from cancer in the next ten years if no action is taken (http://www.who.int/cancer). Obesity appears to play important roles not only in cardiovascular and metabolic diseases, but also in cancer etiology (Bray 2004). For example, overweight and obesity account for 25% of the patients with breast cancer, the most frequent cancer and the second leading cause of cancer death among women (Calle et al. 2003; McTiernan 2003). Excess adiposity over the preand post-menopausal years is an independent risk factor for breast cancer and its relapse (Alokail et al. 2009; Katoh et al. 1994; McTiernan 2005; Saxe et al. 1999), and is associated with late-stage disease and poor prognosis (Lorincz and Sukumar 2006). On the other hand, information is limited on why excess body fat increases cancer risks and how obesity affects the prognosis and therapy of cancer. Dysfunctional adipose tissue, characterized by aberrant production of adipokines, is believed to be a key player in obesity-related mammary carcinogenesis. Adipokines are a family of molecules selectively secreted by fat tissue (Deng and Scherer 2010). In obese subjects, the production of adipokines is dysregulated, which in turn contributes to medical conditions associated with obesity (Galic et al. 2010). Evidence from clinical, epidemiological and experimental studies suggest that adipokines are key pathological mediators in obesityrelated cancer diseases, although the underlying mechanisms remain to be uncovered and may vary from site to site (Prieto-Hontoria et al. 2010; van Kruijsdijk et al. 2009). The present review is to provide a systemic update on how adipokines affect breast cancer cell function and mammary tumor initiation and development. Specifically, the detailed roles of three adipokines [adiponectin, lipocalin-2 and leptin] in mammary carcinogenesis will be discussed by integrating the information derived from cellular, animal and clinical studies.