Can Exosomes Induced by Breast Involution Be Markers for the Poor Prognosis and Prevention of Post-partum Breast Cancer
Abstract
Breast cancers diagnosed up to six years after a completed pregnancy have been referred to as pregnancy-associated breast cancer or PABC. Severalstudies show that PABC frequently metastasizes, resulting in poor prognosis for the patient. Post-partum mammary gland involution is a necessary physiologicprocess required to return the lactation-competent gland to a non-lactating state. Accumulating evidence indicates that tissue-remodeling programs similar towound healing are utilized to remodel the lactating gland to its post-partum state and that these programs are characterized by immune modulation. To movethis work forward into the clinic, further understanding of the complexity between the tumor microenvironment and circulating factors that both influence themetastatic potential of these tumors and compromise the host immune response to the tumor are of great importance. It would also be ideal to have acirculating marker that would both identify women at risk for a postpartum breast cancer (PPBC), as well as, to assess the potential clinical benefit from noveltherapies aimed to reduce the metastatic potential of PPBC. We have therefore undertaken this project to show that extracellular vesicles [EVs] are releasedfrom the actively involuting gland and exist in the circulation during involution that carry pro-metastatic cargo These EVS can also influence tumor microenvironmentinteractions, immune escape, and the metastatic niche. In this proposal, our objectives were to determine, for the first time, whetherexosomes with unique properties can be identified during involution, are likewise present in women with PPBC, and whether anti-inflammatory agent treatmentmitigates their numbers, content, and or function. In completing this work. We have identified important technologic requirements to be able to effectivelystudy the EV proteome from plasma samples of animals and humans, adding significantly to the understanding of translational EV research in cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1035714
Entities
People
- Virginia F Borges
Organizations
- Anschutz Medical Campus