Genetic and mechanistic determinants of prostate cancer progression and metastasis

In order to study a complex biological phenomenon such as tumor cell metastasis, one must focus on examining discrete aspects of the process which are amenable to experimentation. In this thesis, I made use of xenograft and spontaneous in vivo mouse models of prostate cancer to approach this problem from two perspectives. First, I sought to identify genes which were involved with metastasis. Second, I focused on the mechanistic elements involved with tumor cell intravasation into lymphatics. The results from this work have shown that loss of Protein 4.1B, a 4.1/ezrin/radixin/moesin (FERM) domain-containing cytoskeletal protein, is a frequent event in prostate cancer. The significance of this finding was confirmed by experimental ablation of 4.1B, which enhanced tumor progression and metastasis, at least in part, by protecting cells against apoptosis. This thesis has also shown that metastatic dissemination to lymph nodes is mediated primarily by peritumoral lymphatic vessels, which surround the tumor at the invasive margins. In contrast, inhibition of intratumoral lymphatics did not affect metastatic spread, indicating that these vessels were unnecessary for tumor cell dissemination.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Wong, Sunny Y

Advisor dc:contributor.advisor

• Richard O. Hynes.

• 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/1721.1/38626

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38626