The recruitment of stromal cells to the site of tumor formation

Myofibroblasts are an alpha-smooth muscle actin ([alpha]-SMA)-expressing cell type found within human mammary carcinomas, but not in the normal mammary gland. Myofibroblasts can enhance tumor formation by promoting angiogenesis and invasion, and we therefore sought to better understand how myofibroblasts are incorporated into breast carcinomas. By identifying secreted factors that recruit myofibroblasts as well as the physical niche where they originated, we aimed to identify possible therapeutic targets to inhibit their incorporation. Using a newly developed mammary carcinoma model, termed BPLER, we identified CXCL1, VEGF, CCL5, and IL-6 as factors that may be important for the recruitment of myofibroblasts. We tested the ability of CXCL1, VEGF164, or CCL5 to affect tumor formation and induce the incorporation of a-SMApositive cells. We show that the expression in MCF-7-Ras modified human breast cancer cells of VEGF164, but not CXCL1 or CCL5, results in the promotion of primary tumor growth and the increased incorporation of [alpha]-SMA-positive cells. Furthermore, we demonstrate that these a-SMA-positive cells do not correlate with cells expressing CD34, a marker of endothelial cells, suggesting that these cells are not [alpha]-SMA-positive smooth muscle cells. Thus, we propose that VEGF is a critical factor that recruits myofibroblasts to the site of breast cancer formation. In another line of experiments, we examined the source of the [alpha]-SMA-positive cell population recruited to another mammary tumor model, termed BPHER-3.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Saelzler, Matthew P. (Matthew Paul)

Advisor dc:contributor.advisor

• Robert A. Weinberg.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/57520

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/57520