Novel Methods for Detecting Cell Interactions in the Tumor Microenvironment

Project: Research project

Project Details

Description

Dramatic progress has been made in recent years identifying mutational events in tumor cells that[unreadable]
lead to progression to the malignant phenotype. However, it has become apparent that the full[unreadable]
expression of this malignant phenotype is modulated by the tumor microenvironment. In breast[unreadable]
cancers, the topic of this application, this consists of many cell types including fat cells, fibroblasts[unreadable]
and immune cells. In the latter class, macrophages are notable in their abundance and in clinical[unreadable]
studies an increase in their density is correlated with poor prognosis. Research by the PI has shown[unreadable]
that these macrophages play important roles in tumor progression and metastasis. These and[unreadable]
others studies have led us to propose six separate traits whereby macrophages can promote tumor[unreadable]
progression and metastasis. These are chronic inflammation, matrix remodeling, tumor cell[unreadable]
invasion, intravasation, angiogenesis and seeding at distant sites. This led to the hypothesis that[unreadable]
the tumor microenvironment educates macrophages to perform specific tasks. Nevertheless, in[unreadable]
other contexts macrophages can kill tumor cells and present antigens to cytotoxic T cells. This has[unreadable]
led to the concept that tumors evolve to avoid immune destruction and to enhance the trophic roles[unreadable]
of these immune cells. In this proposal in three projects, in human breast cancers and mouse[unreadable]
models we will define the mechanistic interactions between tumor cells, the immune system and[unreadable]
other components of the microenvironment that results in tumor progression and metastasis.[unreadable]
Project 1: Natural History of immune responses in a mouse model of spontaneous breast[unreadable]
cancer. This addresses the hypothesis that the tumor microenvironment biases the local immune[unreadable]
response away from a cytotoxic one to a benign or trophic one through the recruitment of regulatory[unreadable]
T cells and myeloid cells. Project 2; The role of macrophages in breast cancer angiogenesis.[unreadable]
This will define the mechanism that macrophages employ to enhance angiogenesis in the tumor.[unreadable]
Project 3: Novel Methods for Detecting Cell Interactions in the Tumor Microenvironment.[unreadable]
This uses nanotechnology to miniaturize an artificial blood vessel that can in dwell in human tumor[unreadable]
xenografts and ultimately in human tumors that can report on the status of cell collection and[unreadable]
diagnose invasive tumors.[unreadable]
StatusFinished
Effective start/end date9/30/068/31/07

Funding

  • National Cancer Institute: $370,001.00
  • National Cancer Institute

ASJC

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pathology and Forensic Medicine
  • Histology
  • Immunology

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