Can Exosomes Induced by Breast Involution Be Markers for the Poor Prognosis and Prevention of Postpartum Breast Cancer.

摘要

Breast cancers diagnosed up to six years after a completed pregnancy have been referred to as pregnancy-associated breast cancer or PABC. Several studies show that PABC frequently metastasizes, resulting in poor prognosis for the patient. Post-partum mammary gland involution is a necessary physiologic process required to return the lactation-competent gland to a non-lactating state. Accumulating evidence indicates that tissue-remodeling programs similar to wound healing are utilized to remodel the lactating gland to its post-partum state and that these programs are characterized by immune modulation. To move this work forward into the clinic, further understanding of the complexity between the tumor microenvironment and circulating factors that both influence the metastatic potential of these tumors and compromise the host immune response to the tumor are of great importance. It would also be ideal to have a circulating marker that would both identify women at risk for a postpartum breast cancer (PPBC), as well as, to assess the potential clinical benefit from novel therapies aimed to reduce the metastatic potential of PPBC. We have therefore undertaken this project to show , that exosomes with pro-metastatic cargo are released from the actively involuting gland, enter the circulation, and influence tumor-microenvironment interactions, immune escape, and the metastatic niche. In this proposal, our objectives are to determine, for the first time, whether exosomes with unique properties can be identified during involution, are likewise present in women with PPBC, and whether anti- inflammatory agent treatment mitigates their numbers, content, and or function. In year 1 of this project, we have successfully developed the new expertise to reliably isolate exosomes from animal plasma from tumor bearing and non-bearing hosts and have performed a rigorous methods comparison to ensure ideal assays are being subsequently performed.