NTTS 2017

Postpartum breast cancers, defined as breast cancers diagnosed within 5-10 years of last childbirth, are nearly twice as likely to become metastatic; this devastating diagnosis affects thousands of young women annually. In pre-clinical models of postpartum breast cancer we have shown that tumor growth, invasion, lymph vessel density (LVD), lymphovascular invasion (LVI), and lymph node (LN) and lung metastasis are increased when breast tumor cells are implanted into postpartum mouse mammary glands compared to those in nulliparous mice. In addition, we revealed increased LVD and LN metastasis in postpartum patients (Lyons, TR et al., Nat Med 2011 and JCI 2014). We identified Sem7a protein as increased in postpartum breast cancer patient samples. In addition, SEMA7A mRNA expression is 3-fold higher in breast tumor tissue compared to normal and SEMA7A expression is associated with decreased overall and distant metastasis free survival, as well as with increased LVI in large patient datasets (Black, S…Lyons, TR, Oncogene 2016). Using silencing and overexpression approaches we observe that growth, invasion, LVD, LVI, as well as LN and lung metastasis are dependent on Sem7a. In addition, we observe that Sem7a is important for adhering to lymphatic endothelial mono-layers and survival in non-adherent conditions. Cumulatively, our results suggest that Sem7a supports multiple steps in the metastatic cascade. As such, we propose that Sem7a is a driver of metastasis for postpartum patients and a risk factor for metastasis in non-postpartum patients and therefore should be explored as a biomarker and therapeutic target.