Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer

Hwang, Shin; Kim, Kwang Man; Cheong, Jae‐Ho; Kim, H.I.; An, Ji Yeong; Hyung, Woo Jin; Noh, Sung Hoon

doi:10.1016/j.ejso.2012.04.009

Cited by 76 publications

(56 citation statements)

References 18 publications

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“…Furthermore, our data suggest that these clinical observations might be mechanistically related to the well-known association of elevated platelet counts and platelet activation with poor prognosis (43)(44)(45)(46)(47)(48)(49)(50). Our study also indicates that pharmacological antagonists of CXCR2 may prevent the establishment of metastases by impairing signaling from platelet-derived CXCL5/7 and the formation of the early metastatic niche.…”

Section: Discussionmentioning

confidence: 58%

Platelets guide the formation of early metastatic niches

Labelle

Begum

Hynes

2014

Proc. Natl. Acad. Sci. U.S.A.

466

408

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During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments ("niches") that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively, host cell-to-host cell interactions may guide the formation of these prometastatic microenvironments. Here, we show that platelet-derived rather than tumor cell-derived signals are required for the rapid recruitment of granulocytes to tumor cells to form "early metastatic niches." Granulocyte recruitment relies on the secretion of CXCL5 and CXCL7 chemokines by platelets upon contact with tumor cells. Blockade of the CXCL5/7 receptor CXCR2, or transient depletion of either platelets or granulocytes prevents the formation of early metastatic niches and significantly reduces metastatic seeding and progression. Thus, platelets recruit granulocytes and guide the formation of early metastatic niches, which are crucial for metastasis. Interactions between host cells and tumor cells both at the primary and metastatic sites are crucial for efficient metastasis (1-3). At the site of metastasis, host cell-tumor cell cross talk contributes to the formation of a metastatic niche, a specialized microenvironment necessary for disease progression. Leukocytes, in particular monocytes and macrophages, have been shown to be recruited to metastatic niches and to support metastasis (4-10). Mechanistically, macrophages secrete VEGFA that facilitates tumor cell extravasation (4). In addition, interaction of monocytes/ macrophages with tumor cells via VCAM1 can prevent tumor cell apoptosis and allow reinitiation of growth at the metastatic site (8, 9). Granulocytes have also been reported to interact with tumor cells and facilitate metastatic seeding possibly by enhancing tumor cell arrest and extravasation (11-13). However, granulocytes exposed to specific environmental stimuli can kill metastatic tumor cells, suggesting that their role in metastasis is highly context dependent (14, 15).Platelets, which interact with tumor cells during their transit through the circulation, also enhance metastasis via multiple mechanisms (3, 16). Metastatic tumor cells can express high levels of tissue factor (TF) and adhesion molecules, such as P-selectin ligands, through which they bind to and activate platelets (16). These interactions result in the formation by platelets of a physical shield around tumor cells, which prevents attacks from natural killer (NK) cells and promotes tumor cell adhesion to the endothelium (17-19). In addition, platelets also promote tumor cell extravasation by increasing endothelial permeability and by directly signaling to tumor cells to enhance their invasive and metastatic potential (20,21). In particular, direct contact between platelets and tumor cells triggers the TGFβ1 and NF-κB signaling pathways in tumor cells, which induce an epithelial-mesenchymal transition and promote metastasis (20). Given their important signa...

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Section: Discussionmentioning

confidence: 58%

Platelets guide the formation of early metastatic niches

Labelle

Begum

Hynes

2014

Proc. Natl. Acad. Sci. U.S.A.

466

408

View full text Add to dashboard Cite

show abstract

“…Previous studies showed that the increased platelet count was associated with poor prognosis in nasopharyngeal carcinoma (Gao et al, 2013), gastric cancer (Hwang et al, 2012), colorectal cancer (Lin et al, 2012), and endometrial carcinomas (Gorelick et al, 2009). Our study found that the elevated values of platelet-based indices predicted poor survival for HCC patients after resection, which was consistent with the findings in other cancers.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Evaluation of Categorical Platelet-based Indices Using Clustering Methods Based on the Monte Carlo Comparison for Hepatocellular Carcinoma

Guo

Shen²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Aliustaoglu et al (2010) and Ikeda et al (2002) analyzed a relatively small number of patients while Heras et al (2010) analyzed only a short-term mortality rate without delineating the prevalence of thrombocytosis in gastric cancer patients. Based on a larger group, Hwang et al (2012) focused on the association between thrombocytosis and hematogenous recurrence. However, undetailed TNM staging and group division in statistic analysis reduced the study's reference meanings in the thrombocytosis research.…”

Section: Significance Of Thrombocytosis In Clinicopathologic Charactementioning

confidence: 99%

“…Previous studies have showed that thrombocytosis is associated with later stage, lymphatic and blood-borne metastasis and higher risk of recurrence in many cancers (Gao et al, 2013;Sasaki et al, 2012;Unal et al, 2013). It was also suggested that patients with thrombocytosis usually inclined to poorer prognoses in ovarian cancer , renal cell carcinoma (Cho et al, 2011), colorectal cancer and gastric cancer (Hwang et al, 2012). Although, several mechanisms of platelet action in facilitating cancer progression and metastasis have been supposed, exact pathophysiological mechanisms of it have not been completely elaborated.…”

Section: Introductionmentioning

confidence: 99%

Significance of Thrombocytosis in Clinicopathologic Characteristics and Prognosis of Gastric Cancer

Wei

Zhang

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Purpose: We aimed to study the relationship between thrombocytosis and clinical features of gastric cancerfocussing on platelet counts and gastric cancer progression through different TNM stages. Methods: According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, >400×1000/μL) and a control group (1,476 patients, ≤400×1000/μL). Results: The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. Conclusion: Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.

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Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer

Cited by 76 publications

References 18 publications

Platelets guide the formation of early metastatic niches

Platelets guide the formation of early metastatic niches

Prognostic Evaluation of Categorical Platelet-based Indices Using Clustering Methods Based on the Monte Carlo Comparison for Hepatocellular Carcinoma

Significance of Thrombocytosis in Clinicopathologic Characteristics and Prognosis of Gastric Cancer

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