Comparison of tumor and microenvironment secretomes in plasma and in platelets during prostate cancer growth in a xenograft model.
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.
Kerr
Bethany A
BA
Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland, OH, USA.
Miocinovic
Ranko
R
Smith
Armine K
AK
Klein
Eric A
EA
Byzova
Tatiana V
TV
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
D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha
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