Comparison of Tumor and Microenvironment Secretomes in Plasma and in Platelets during Prostate Cancer Growth in a Xenograft Model

Kerr, Bethany A.; Miocinovic, Ranko; Smith, Arthur L.; Klein, Eric A.; Byzova, Tatiana V.

doi:10.1593/neo.10166

Cited by 34 publications

(34 citation statements)

References 46 publications

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“…Interest in platelets and their ability to interact with intravascular components have enticed several groups to pursue the use of platelets as a protein source for cancer biomarkers and investigating their function in disease. [18][19][20][21][22] Several platelet proteins were identified as potential cancer biomarkers, including PF4 23 and thrombospondin-1. 24 Interestingly, thrombospondin-1 was shown to be a negative regulator of angiogenesis and affects plateletmediated recruitment of bone marrow-derived cells to sites of tumor angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Blood platelets contain tumor-derived RNA biomarkers

Nilsson

Balaj

Hulleman

et al. 2011

Blood

321

302

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Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer. (Blood. 2011;118(13):3680-3683)

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Section: Discussionmentioning

confidence: 99%

Blood platelets contain tumor-derived RNA biomarkers

Nilsson

Balaj

Hulleman

et al. 2011

Blood

321

302

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“…3,4 Kerr and colleagues showed that many tumor-secreted proteins are taken up and stored in platelets and specifically released at the metastatic sites. 13 However, while the ability of cancer cells to aggregate and cluster platelets around the tumor is supported by a large body of experimental and clinical data, 32,45,46 the role of cancer cells in promoting platelet secretion of procarcinogenic and thrombotic factors is poorly understood. In the present study, we show that highly metastatic colorectal cancer cells (Caco-2) and a prostate carcinoma cell line (PC3M-luc) stimulate the release of plateletdense granule contents in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, platelet a-granules contain large reservoirs of cytokines and growth factors, including transforming growth factor b (TGF-b) and vascular endothelial growth factor (VEGF), 10,11 which are selectively released upon platelet activation. 12,13 Consistent with a role of platelet secretion in tumor metastasis, TGF-b derived from platelet a-granules has been shown to profoundly impact tumor metastasis and survival by enhancing an epithelial mesenchymal-like transition and suppressing tumor cell natural killer-mediated lysis, respectively. 2,3 Moreover, platelet secretion in a tumorigenic microenvironment seems to differ materially from wound-induced platelet secretion.…”

Section: Introductionmentioning

confidence: 85%

A novel and essential role for FcγRIIa in cancer cell–induced platelet activation

Mitrugno

Williams

Kerrigan

et al. 2014

Blood

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Key Points• The immune receptor FcgRIIa is a key mediator of tumor cell activation of platelets in the circulation.• Secretion of adenosine 59-diphosphate from dense granules is the primary response of platelets to activation by tumor cells.Platelets play a role in cancer by acting as a dynamic reservoir of effectors that facilitate tumor vascularization, growth, and metastasis. However, little information is available about the mechanism of tumor cell-induced platelet secretion (TCIPS) or the molecular machinery by which effector molecules are released from platelets. Here we demonstrate that tumor cells directly induce platelet secretion. Preincubation of platelets with human colon cancer (Caco-2), prostate cancer (PC3M-luc), or breast cancer cells (MDA-MB-231;MCF-7) resulted in a marked dose-dependent secretion of dense granules. Importantly, TCIPS preceded aggregation which always displayed a characteristic lag time. We investigated the role of platelet receptors and downstream molecules in TCIPS. The most potent modulators of TCIPS were the pharmacologic antagonists of Syk kinase, phospholipase C and protein kinase C, all downstream mediators of the immunoreceptor tyrosine-based activation motif (ITAM) cascade in platelets. Supporting this, we demonstrated a central role for the immune Fcg receptor IIa (FcgRIIa) in mediating platelet-tumor cell cross-talk. In conclusion, we demonstrate that cancer cells can promote platelet dense-granule secretion, which is required to augment platelet aggregation. In addition, we show a novel essential role for FcgRIIa in prostate cancer cell-induced platelet activation opening the opportunity to develop novel antimetastatic therapies. (Blood. 2014;123(2):249-260)

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“…Analyses of the complete set of secreted proteins -otherwise known as the "secretome" -have been reported in various organisms, cell types, and pathologies, and are quickly gaining popularity [6,7]. Not surprisingly, several studies have focused on analyses of cancer-or metastasis-specific changes in secretome profiles [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, none of the studies to date has focused on secretomes relevant to the bone metastasis phenotype.…”

Section: Introductionmentioning

confidence: 99%

Global secretome analysis identifies novel mediators of bone metastasis

et al. 2012

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Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

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Comparison of Tumor and Microenvironment Secretomes in Plasma and in Platelets during Prostate Cancer Growth in a Xenograft Model

Cited by 34 publications

References 46 publications

Blood platelets contain tumor-derived RNA biomarkers

Blood platelets contain tumor-derived RNA biomarkers

A novel and essential role for FcγRIIa in cancer cell–induced platelet activation

Global secretome analysis identifies novel mediators of bone metastasis

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