Abstract：
:Tumor development relies upon essential contributions from the tumor microenvironment and host immune alterations. These contributions may inform the plasma proteome in a manner that could be exploited for cancer diagnosis and prognosis. In this study, we employed a systems biology approach to characterize the plasma proteome response in the inducible HER2/neu mouse model of breast cancer during tumor induction, progression, and regression. Mass spectrometry data derived from approximately 1.6 million spectra identified protein networks involved in wound healing, microenvironment, and metabolism that coordinately changed during tumor development. The observed alterations developed prior to cancer detection, increased progressively with tumor growth and reverted toward baseline with tumor regression. Gene expression and immunohistochemical analyses suggested that the cancer-associated plasma proteome was derived from transcriptional responses in the noncancerous host tissues as well as the developing tumor. The proteomic signature was distinct from a nonspecific response to inflammation. Overall, the developing tumor simultaneously engaged a number of innate physiologic processes, including wound repair, immune response, coagulation and complement cascades, tissue remodeling, and metabolic homeostasis that were all detectable in plasma. Our findings offer an integrated view of tumor development relevant to plasma-based strategies to detect and diagnose cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Pitteri SJ,Kelly-Spratt KS,Gurley KE,Kennedy J,Buson TB,Chin A,Wang H,Zhang Q,Wong CH,Chodosh LA,Nelson PS,Hanash SM,Kemp CJdoi
10.1158/0008-5472.CAN-11-0568subject
Has Abstractpub_date
2011-08-01 00:00:00pages
5090-100issue
15eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-0568journal_volume
71pub_type
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