Accession Number : AD1002228


Title :   Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis


Descriptive Note : Technical Report,01 Sep 2014,31 Aug 2015


Corporate Author : University of Wisconsin - Madison Madison United States


Personal Author(s) : Aguirre-Ghiso,Julio A ; Condeelis,John


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1002228.pdf


Report Date : 01 Sep 2015


Pagination or Media Count : 80


Abstract : Understanding early dissemination and early DTC behavior is important because we found that DCIS lesions produce large amounts of early DTCs that are dormant. This could contribute silently to therapy resistance and late metastatic relapse. Unfortunately, these events have remained understudied because of lack of tools. Our collaboration, which brings new tools, has allowed us to explore these mechanisms to gather this highly significant and transformative knowledge. We believe that our proposal will provide answers to the overarching challenge to Determine why/how breast cancer cells lay dormant for years and then re-emerge (recurrence); determine how to eliminated dormant cells early. We proposes the existence of a structure called tumor microenvironment of metastasis or TMEM, which is composed by a specialized macrophage a tumor cell also specialized and the endotghelium1. We detected primary tumor or P-TMEM (previously only detected in invasive cancers) in pre-malignant lesions1. The P-TMEM is required to induce an EMT and early dissemination of premalignant MECs. We further hypothesize that after extravasation at S-TMEM, in order to exit dormancy a stable S-TMEM structure needs to be maintained and that early DTCs cannot sustain its assembly possibly because they lack a persistent M recruiting program. Our rationale is that by understanding early dissemination and dormancy of DTCs we will find ways to eradicate dormant DTCs and prevent metastasis. Our original specific aims are 1. Test how ErbB2 sup high/P-p38 sup low MECs assemble P-TMEM during early dissemination. 2. Test the role of S-TMEM in regulating early DTC dormancy. In this progress report we provide novel evidence supporting our aims and hypothesis.


Descriptors :   breast cancer , Dormancy , Macrophages , metastasis , neoplasms , CELLULAR MICROENVIRONMENT , cancer research


Distribution Statement : APPROVED FOR PUBLIC RELEASE