Extra Cellular Matrix Proteins and Cancer

Technology 

Current invention uses quantitative mass spectrometric profiling of ECM proteins of non-metastatic primary tumors and metastatic tumors compared to normal tissue. This allowed for generation of signature sets of ECM proteins that are deregulated in tumors and also between different progression stages of cancer. These signature sets can be used to profile progression stage of cancer biopsies. Using antibodies targeted against the proteins in the signature sets, it is also possible to deliver conjugated agents such as imaging agents or chemotherapeutic agents for imaging and treatment of cancer. 

Problem Addressed

Large data sets of mutations, gene expression, and protein expression have been generated to understand the biology and progression of cancer with the hopes of identifying ways to treat cancer. However, understanding the role of ECM in disease progression using ECM as a way to target cancer has been mostly limited. This is because ECM proteins are insoluble and are crosslinked, thus, are intractable for large scale protein analysis. The current invention utilizes recently developed proteomic methods to identify ECM signatures associated with cancer and its progression, which can be used to diagnose, prognose, and treat cancer.    

Advantages  

• Cancer-related ECM signatures identifies targets that are significantly enriched in tumors compared to normal tissue, which can be used to diagnose and prognose cancer
• Proteins in ECM signatures can be targeted using conjugated antibodies, thus, limiting systemic exposure 

Publications

Naba, Alexandra, Karl R. Clauser, Hiroshi Tanaka, Shana A. Hynes, Haydee M. Estrada, Junmin Hu, Saghi Q. Afjehi-Sadat, et al. "The Matrisome: In Silico Definition and In Vivo Characterization by Proteomics of Normal and Tumor Extracellular Matrices." Molecular & Cellular Proteomics 11, no. 4 (April 2012): M111.014647. doi:10.1074/mcp.M111.014647. Published online December 9, 2011.

Oskarsson, Therese, Mona Acharyya, Xiaoyan Zhang, Quang-De Nguyen, David G. Norton, et al. "Extracellular Matrix Signatures of Human Mammary Carcinoma Identify Novel Metastasis Promoters." eLife 3 (March 11, 2014): e01308. doi:10.7554/eLife.01308.

Naba, Alexandra, Karl R. Clauser, Shana A. Hynes, Johanna P. Enloe, Hiroshi Tanaka, et al. "Extracellular Matrix Signatures of Human Primary Metastatic Colon Cancers and Their Metastases to Liver." BMC Cancer 14 (July 18, 2014): 518. doi:10.1186/1471-2407-14-518.