Tumor microenvironment-derived proteins dominate the plasma proteome response during breast cancer induction and progression.
Tumor microenvironment-derived proteins dominate the plasma proteome response during breast cancer induction and progression.
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DOI：
10.1158/0008-5472.can-11-0568
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发表时间：
2011-08-01
期刊：
影响因子：
11.2
通讯作者：
Kemp CJ
中科院分区：
文献类型：
--
作者：
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 CJ
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 ∼ 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 non-cancerous host tissues as well as the developing tumor. The proteomic signature was distinct from a non-specific response to inflammation. Overall, the developing tumor simultaneously engaged a number of innate physiological 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 with relevance to plasma-based strategies to detect and diagnose cancer.
