Pretreatment Thrombocytosis as a Prognostic Factor in Metastatic Breast Cancer

Stravodimou, Athina; Voutsadakis, Ioannis A.

doi:10.1155/2013/289563

Cited by 43 publications

(31 citation statements)

References 27 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: Discussionsupporting

confidence: 61%

Platelets guide the formation of early metastatic niches

Labelle

Begum

Hynes

2014

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

455

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: Discussionsupporting

confidence: 61%

Platelets guide the formation of early metastatic niches

Labelle

Begum

Hynes

2014

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

455

408

View full text Add to dashboard Cite

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“…In their study on patients with a platelet count of less than 450,000/mm 3 , the 5-y survival rate was 70%, compared with 38% when the platelet count was 450,000/mm 3 or greater. The negative impact of thrombocytosis on prognosis has been also reported in other cancer types, such as bladder cancer (20), gynecologic malignancies (21)(22)(23), and gastrointestinal cancers (24), as well as in early and advanced breast cancer (25,26). According to different published studies, cytokines, in particular IL-6, play an important role in the development of thrombopoiesis and thrombocytosis (22)(23)(24).…”

Section: Discussionmentioning

confidence: 87%

Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with ¹⁷⁷Lu-PSMA-617

et al. 2016

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Radioligand therapy (RLT) with 177 Lu-PSMA-617 (PSMA is prostatespecific membrane antigen) is a novel targeted therapy for metastatic prostate cancer. In this study, we evaluated the effect of different pretherapeutic parameters on the therapeutic response measured by prostate-specific antigen (PSA) 2 mo after RLT. Methods: RLT was performed in 40 hormone-refractory patients with distant metastases and progressive disease (mean age, 71.4 y). 68 Ga-PSMA-11 PET/CT was performed in all patients 1-2 wk before RLT. All patients were treated with a mean of 6 GBq. The SUV max of tumor lesions was determined using region-of-interest analysis. Complete blood counts, renal and liver function assessments, previous therapies, pain medication, and SUVs were included in the analysis. PSA was assessed 2 mo after RLT. Results: In the univariate analysis, younger age, higher levels of g-glutamyl transferase, lower pretherapeutic hemoglobin, a higher Gleason score, a higher number of platelets, higher C-reactive protein, regular need for pain medication, and higher lactate dehydrogenase had a negative impact on the therapeutic response; however, the multivariate analysis revealed that the most significant independent factors were the number of platelets and regular need for pain medication. The response was independent of the amount of PSMA uptake as well as previous therapies and other measured factors. Conclusion: A PSA decline of more than 50% was observed significantly more in patients without a regular need for analgesics.

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“…This is supported by the fact that poor prognosis in both breast and head/neck cancers have been demonstrated to have a direct correlation with elevations in both interleukin‐6 and platelet counts (Agoston et al, ; Benoy et al, ). It is theorized that tumor‐burden‐associated paraneoplastic production of interleukin‐6 stimulates hepatocyte production of thrombopoietin, which in turn amplifies bone marrow platelet production (Stravodimou & Voutsadakis, ). It should also be considered that excess platelets have been proposed to conceal circulating tumor cells from the body's immune system and enable enhanced tumor cell metastasis (Stravodimou & Voutsadakis, ; Taucher et al, ).…”

Section: Discussionmentioning

confidence: 99%

Thrombocytosis is associated with complications after microvascular surgery: An NSQIP data analysis

et al. 2019

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Background Complications after microvascular surgery, such as partial flap loss, and arterial/venous compromise cannot only increase morbidity for the patient but also tax the healthcare system. Thrombocytosis, both essential and reactive, can predispose patients to thrombosis and hemorrhage and thus should intuitively have an effect on the outcome of microvascular free tissue transfers. We sought to evaluate the effect of preoperative thrombocytosis on outcomes after microvascular free flap surgery. Methods A retrospective review of the 2013–2016 American Collges of Surgeons, National Surgical Quality Improvement Program (ACS NSQIP) database identified 4,299 patients who had microsurgical flaps. Of these 3,744 had preoperative platelet levels recorded. Fifty‐four patients had preoperative thrombocytosis, defined as a platelet count >450 K/CUMM, while 3,690 did not. The groups were compared; demographics, comorbidities, and smoking status were recorded. We then examined outcomes between groups including average operative time, length of hospital stay, need for transfusion, deep vein thrombosis (DVT) postoperatively, and need for reoperation. Results When comparing the two cohorts, there was no statistical difference in comorbidities. We found a significant difference between the thrombocytosis and control cohort in need for transfusion (29.6 vs. 12.8%, p = .0002), average days till discharge (8.36 vs. 5.75, p = .009), and need for reoperation (27.8 vs. 13.8%, p = .003). There was no difference in DVT occurrence (0 vs. 0.1%, p = .46) or average operation time (535 m vs. 482 min, p = .088). Conclusion Patients with thrombocytosis undergoing microvascular free flaps are at increased risk for complications, including the need for a blood transfusion, prolonged hospital stays, and reoperation.

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Pretreatment Thrombocytosis as a Prognostic Factor in Metastatic Breast Cancer

Cited by 43 publications

References 27 publications

Platelets guide the formation of early metastatic niches

Platelets guide the formation of early metastatic niches

Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with ¹⁷⁷Lu-PSMA-617

Thrombocytosis is associated with complications after microvascular surgery: An NSQIP data analysis

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Pretreatment Thrombocytosis as a Prognostic Factor in Metastatic Breast Cancer

Cited by 43 publications

References 27 publications

Platelets guide the formation of early metastatic niches

Platelets guide the formation of early metastatic niches

Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with 177Lu-PSMA-617

Thrombocytosis is associated with complications after microvascular surgery: An NSQIP data analysis

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Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with ¹⁷⁷Lu-PSMA-617