Role of Lactoferrin in the Carcinogenesis of Triple-Negative Breast Cancer.

Lactoferrin is a ubiquitous, secretory, iron binding glycoprotein found in exocrine secretions such as saliva, pancreatic secretions and bile of mammals, including humans. It is considered a member of the transferrin family due to a close resemblance in molecular structure and size. Lactoferrin is produced in neutrophils and stored in specific granules. Its secretion from polymorphonuclear cells into circulation is dependent on the activation of guanylate cyclase, cGMP and protein kinase C. Lactoferrin gene expression is modulated by the steroidthyroid receptor superfamily, indicating that it is a hormone responsive gene. Lactoferrin is reported to have a variety of biological functions, including DNA synthesis, immune responses, iron transport, antimicrobial action, RNase activity, transcriptional activating functions, and receptor-mediated lipid uptake, any of which could play a role in tumor promotion [1-12]. Being a hormone responsive gene, lactoferrin may contribute to various hormone dependent cancers such as breast cancer and cancers of the female reproductive tract. In this context, it is important to note that an earlier report has shown an inverse relationship with the level of estrogen receptor and lactoferrin [13,14]. It was also found that lactoferrin and steroid hormone receptor expression are down regulated in adenocarcinomas of the endocervix, which may be associated with the loss of differentiation during neoplastic transformation [14]. Lactoferrin expression, similar to endocervix, is highly expressed in women’s normal resting and lactating breasts, but seems to be progressively downregulated in many breast cancers.