title: Comparison of tumor and microenvironment secretomes in plasma and in platelets during prostate cancer growth in a xenograft model.
abstract: To survive and metastasize, tumors interact with surrounding tissues by secreting growth factors and cytokines. In return, surrounding host tissues respond by changing their secretome. Numerous factors theoretically function as therapeutic targets or biomarkers of cancer growth and metastatic risk. However, it is unclear if these factors are tumor-derived or actually represent the host defense. To analyze the concentrations of tumor- and microenvironment-derived factors associated with neoplastic growth, we used ELISA-based arrays specific for murine or human proteins to establish a profile of tumor- or host-derived factors circulating in the plasma or within the platelets upon human tumor implantation into mice. Many factors characterized as tumor-derived were actually secreted by host tissues. This study uncovered the origin of various cytokines and revealed their circulation methods. We found that tumor-produced cytokines are predominantly sequestered in platelets. Sequestered proteins are protected from degradation and, thus, may be functional at metastatic sites. These findings identify tumor-specific targets for the detection and prevention of tumor growth and metastasis. As predicted by our model, monocyte chemotactic protein 1 and tumor necrosis factor alpha may be biomarkers for human cancers. Thus, our study identified several potential biomarkers that might be predictive of prostate cancer.
authors.affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland, OH, USA.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Kerr
authors.forename: Ranko
authors.initials: R
authors.lastname: Miocinovic
authors.forename: Armine K
authors.initials: AK
authors.lastname: Smith
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Byzova
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011471:Prostatic Neoplasms / Q000097:blood*; D040081:Protein Array Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha
references.citation: Anticancer Res. 2005 Nov-Dec;25(6B):3963-6
references.pmid: 16309184
references.citation: Thromb Haemost. 2007 Nov;98(5):922-9
references.pmid: 18000594
references.citation: Cell. 2005 May 6;121(3):335-48
references.pmid: 15882617
references.citation: J Cell Biol. 1993 Aug;122(4):923-32
references.pmid: 8349738
references.citation: Int J Mol Med. 2006 Nov;18(5):941-50
references.pmid: 17016625
references.citation: Cancer Res. 2009 Jan 1;69(1):329-37
references.pmid: 19118018
references.citation: Neoplasma. 2007;54(4):285-9
references.pmid: 17822317
references.citation: J Biol Chem. 1997 Oct 24;272(43):27183-8
references.pmid: 9341161
references.citation: Eur J Cancer. 2003 Sep;39(13):1948-56
references.pmid: 12932675
references.citation: J Clin Oncol. 2001 Jun 1;19(11):2856-64
references.pmid: 11387358
references.citation: Cancer Res. 2009 Apr 15;69(8):3433-42
references.pmid: 19351846
references.citation: J Clin Invest. 1988 Apr;81(4):1012-9
references.pmid: 3280598
references.citation: Nature. 2003 May 15;423(6937):337-42
references.pmid: 12748652
references.citation: Ann N Y Acad Sci. 2007 Nov;1116:392-413
references.pmid: 18083941
references.citation: Nature. 2006 Mar 30;440(7084):692-6
references.pmid: 16572175
references.citation: Urol Res. 2005 Feb;33(1):44-50
references.pmid: 15517230
references.citation: Expert Rev Anticancer Ther. 2007 Feb;7(2):221-32
references.pmid: 17288531
references.citation: Br J Cancer. 2008 Feb 26;98(4):809-15
references.pmid: 18253114
references.citation: J Urol. 1999 Jan;161(1):182-7
references.pmid: 10037394
references.citation: Clin Cancer Res. 1999 Mar;5(3):487-91
references.pmid: 10100697
references.citation: Blood. 2009 Mar 19;113(12):2835-42
references.pmid: 19036702
references.citation: Biomarkers. 2008 Mar;13(2):217-36
references.pmid: 18270872
references.citation: Cancer Res. 2008 Jan 1;68(1):323-8
references.pmid: 18172326
references.citation: J Exp Med. 2006 May 15;203(5):1221-33
references.pmid: 16618794
references.citation: Int J Cancer. 2006 Jul 1;119(1):146-51
references.pmid: 16450378
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3352-7
references.pmid: 11248082
references.citation: Oncology. 2008;75(3-4):230-6
references.pmid: 18852494
references.citation: Cancer Res. 2008 Aug 15;68(16):6851-8
references.pmid: 18701510