Identification of a novel metastasis enhancer, CDCP1, and analysis of its functions during melanoma metastasis

Nearly 90% of cancer mortality from solid tumors is due to metastasis of malignant cells to the distant vital organs. It is now well established that a plethora of stromal cells are present within the tumor, and contribute in various ways to tumor initiation and progression, and plasma membrane proteins are the mediators for tumor-stromal communications. In this thesis, I focused on plasma membrane proteins that may contribute to tumor metastasis. I applied quantitative mass spectrometry technology to first identify plasma proteins that are expressed at different levels in melanoma cells with high versus low metastatic abilities. Using SILAC (stable isotope labeling with amino acids in culture) coupled with nano-spray tandem mass spectrometry, this work led to the discovery of C̲ub Ḏomain C̲ontaining Protein 1 (CDCP1) as one of those differentially expressed transmembrane proteins. We found that CDCP1 is not only a surface marker for cells with higher metastatic potential, it is also functionally engaged in enhancing tumor metastasis. When searching for the underlying mechanisms, we found that CDCP1 is important for soft agar colony-forming abilities, suggesting that CDCP1 might regulate the balance between cell proliferation and anoikis. Making use of 3D Matrigel culture system, we found that CDCP1 also regulates scattered growth of melanoma cells. We speculate these two factors may contribute to enhanced-metastatic ability observed in mice.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Liu, Hui

Advisor dc:contributor.advisor

• Richard O. Hynes and Forest M. White.

• 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/1721.1/47881

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/47881