Platelets, coagulation and fibrinolysis in breast cancer progression

Lal, Inder; Dittus, Kim; Holmes, Chris E.

doi:10.1186/bcr3425

Cited by 126 publications

(124 citation statements)

References 81 publications

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“…Cancer cells were shown to have the ability to interact with platelets in vitro several decades ago (19)(20)(21)(22). Furthermore, the interaction between circulating tumor cells (CTCs) and circulating platelets is now recognized as a hallmark of the metastatic potential of cancer (6,8). Recent studies have demonstrated that the presence of platelet aggregation around tumor cells can be detected both in the circulation and in primary tumor cells in patients with pancreatic cancer (23).…”

Section: Discussionmentioning

confidence: 99%

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Platelets surrounding primary tumor cells are related to chemoresistance

et al. 2016

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Abstract.Platelets are crucial components of the tumor microenvironment that function to promote tumor progression and metastasis. In the circulation, the interaction between tumor cells and platelets increases invasiveness, protects tumor cells from shear stress and immune surveillance, and facilitates tumor cell extravasation to distant sites. However, the role and presence of platelets in the primary tumor have not been fully determined. Here, we investigated the presence of platelets around breast cancer primary tumor cells and the associations between these cells. We further investigated the associations among platelets, tumor cells, chemoresistance, and epithelial-mesenchymal transition (EMT). We retrospectively analyzed data from 74 patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer who underwent biopsies before treatment and subsequent neo-adjuvant chemotherapy. In biopsy specimens, we evaluated the expression of platelet-specific markers and EMT markers using immunohistochemistry. The associations among the expression of platelet-specific markers in biopsy specimens, EMT, response to neo-adjuvant chemotherapy, and survival were analyzed. The presence of platelets was observed in 44 out of 74 (59%) primary breast cancer biopsy specimens. Platelet-positive tumor cells showed EMT-like morphological changes and EMT marker expression. Primary tumor cells associated with platelets were less responsive to neo-adjuvant chemotherapy (pCR rate: 10 vs. 50%, respectively; p=0.0001). Platelets were an independent predictor of the response to chemotherapy upon multivariable analysis (p<0.0001). In conclusion, there was a significant association between platelets surrounding primary tumor cells in the biopsy specimens and the chemotherapeutic response in breast cancer. Platelets surrounding primary tumor cells may represent novel predictors of chemotherapeutic responses.

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Section: Discussionmentioning

confidence: 99%

“…Platelets, the smallest anucleate hematopoietic cells, are now recognized as key regulators of tumor progression and metastasis (6)(7)(8). In the circulation, platelet aggregation protects cancer cells from shear stress and immune surveillance through the formation of a platelet cloak.…”

Section: Introductionmentioning

confidence: 99%

Platelets surrounding primary tumor cells are related to chemoresistance

et al. 2016

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“…In this review, we summarize the recent progress in breast cancer biology associated with aberrant coagulation mechanisms. In particular, we focus on the TF-fVII pathway, among the multiple coagulation mechanisms, because breast cancer phenotypes associated with platelets and fibrinolysis have been extensively reviewed [17] . We also describe the mechanisms underlying TF and fVII overexpression and how their functions may be regulated in breast cancer cells.…”

Section: Topic Highlightmentioning

confidence: 99%

Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

Koizume

Miyagi

2014

WJCO

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Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII (fVII) is produced in the liver and secreted into the blood stream. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fVII complex may be formed in the absence of injury, because fVII potentially exists in the tissue fluid within cancer tissues. The active form of this complex (TF-fVIIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fVII pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mechanisms by which TF-fVII signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fVII synthesis and regulation in breast cancer cells. Our current understanding of the TF-fVII pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies. Key words: Breast cancer; Blood coagulation; Tissue factor; Coagulation factor VII; Gene regulation; Therapeutic strategy Core tip: Breast cancer is a worldwide problem. Difficulties with treating the disease and its recurrence persist due, in part, to a lack of therapeutic molecular targets. Blood coagulation factor VII (fVII) is generally produced in the liver. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. Formation of the TF-fVII complex causes contributes to the malignant phenotype of breast cancer cells. In this review, we summarize the breast cancer biology associated with the TF-fVII pathway. Further, we will discuss how these mechanisms can be targeted as therapeutics for this aggressive disease.Koizume S, Miyagi Y. Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets.

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“…Platelets are important in tumour cell migration [3] and experimental data have shown that aspirin can inhibit platelet-induced adhesion of circulating tumour cells [4], and prevent metastases formation [5]. In breast cancer specifically, both in vitro and animal models demonstrate anti-angiogenic [6] and pro-apoptotic [7] effects for aspirin, as well as the suppression of tumour cell extravasation and tissue invasion [8].…”

Section: Introductionmentioning

confidence: 99%