Compressive stress enhances coordinated migration of mammary carcinoma cells

Cancer research has traditionally focused on genetic and biochemical changes during tumor progression. Uncontrolled cell proliferation of a solid tumor in a confined space not only creates well-studied oxidative stress (hypoxia), but also generates growth-induced mechanical stress (compression). However, the importance of such compressive stress in tumor biology has been largely ignored. Our lab has previously shown that compressive stress influences tumor spheroid growth and stimulates production of extracellular matrix molecules. Others have also demonstrated the importance of matrix rigidity in tumor development and enhanced tumor cell adhesion by hydrostatic pressure. Yet whether growth-induced compressive stress can enhance caner cell migration and invasion remains unclear. The focus of this thesis is to evaluate the effect of anisotropic compressive stress on cancer cell motility. To mimic growth-induced compressive stress experienced by cancer cells in vivo, we developed an in vitro compression device for compressing a monolayer of cancer cells with precisely-defined normal forces. Here we show, for the first time, that externally-applied compressive stress resulted in faster migration of some mammary carcinoma cell lines. Independent of multi-cellular micro-organization, compression induced migration of mammary carcinoma cells in a coordinated sheet, initiated by "leader cells" -- single cells at the leading edge of the sheet, extending long filopodia.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Tse, Janet M. (Janet Man-Yu)

Advisor dc:contributor.advisor

• Rakesh K. Jain and Robert S. Langer.

• Chemical Engineering.

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/1721.1/57521

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/57521