During tumor progression the well-ordered architecture of the mammary gland becomes disrupted as hyperproliferative cells accumulate in the luminal space of ducts and lobules. Over time the neoplastic cells can invade into the stroma where they can access the vasculature system and disseminate to distant sites throughout the body. Although the induction of invasive growth is a key step in the metastatic cascade, how breast cancer cells become invasive remains poorly understood. Using an organotypic culture system and animal models we propose to determine (1) how cell motility is regulated by intracellular signaling pathways during collective invasion;(2) how mammary fibroblasts induce collective invasion and (3) how subpopulations of neoplastic cells trigger collective invasion. Deciphering the requirements for breast cancer invasion could identify targets for therapeutic intervention in both the tumor and the microenvironment.

Public Health Relevance

Distant metastases are responsible for nearly all breast cancer patient deaths. A critical step leading to the development of metastases is the invasion of tumor cells into connective tissue. We will investigate how tumor cells become invasive with the goals of more accurately identifying which patients are at risk of developing metastases and identifying targets of therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA155241-03
Application #
8445431
Study Section
Tumor Microenvironment Study Section (TME)
Program Officer
Woodhouse, Elizabeth
Project Start
2011-03-01
Project End
2016-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
3
Fiscal Year
2013
Total Cost
$310,130
Indirect Cost
$115,080
Name
University of Texas Sw Medical Center Dallas
Department
Pharmacology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Dang, Tuyen T; Prechtl, Amanda M; Pearson, Gray W (2011) Breast cancer subtype-specific interactions with the microenvironment dictate mechanisms of invasion. Cancer Res 71:6857-66