The Pathogenetic Role of Apoptosis in Hypercoagulable States

Wang, Jun; Kwaan, Hau C.

doi:10.1080/10245332.2001.11746565

Cited by 2 publications

(2 citation statements)

References 85 publications

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“…Our findings bolster the concept that apoptotic cells are an important procoagulant mechanism in various health and disease settings (59). TF activity regulated through phosphatidylserine exposure has been described in other disease contexts such as endotoxemia (60–62) and vessel injury(63,64).…”

Section: Discussionsupporting

confidence: 84%

Apoptotic cells promote circulating tumor cell survival and metastasis

Hagan,

Snyder,

Headley

et al. 2024

Preprint

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During tumor progression and especially following cytotoxic therapy, cell death of both tumor and stromal cells is widespread. Despite clinical observations that high levels of apoptotic cells correlate with poorer patient outcomes, the physiological effects of dying cells on tumor progression remain incompletely understood. Here, we report that circulating apoptotic cells robustly enhance tumor cell metastasis to the lungs. Using intravenous metastasis models, we observed that the presence of apoptotic cells, but not cells dying by other mechanisms, supports circulating tumor cell (CTC) survival following arrest in the lung vasculature. Apoptotic cells promote CTC survival by recruiting platelets to the forming metastatic niche. Apoptotic cells externalize the phospholipid phosphatidylserine to the outer leaflet of the plasma membrane, which we found increased the activity of the coagulation initiator Tissue Factor, thereby triggering the formation of platelet clots that protect proximal CTCs. Inhibiting the ability of apoptotic cells to induce coagulation by knocking out Tissue Factor, blocking phosphatidylserine, or administering the anticoagulant heparin abrogated the pro-metastatic effect of apoptotic cells. This work demonstrates a previously unappreciated role for apoptotic cells in facilitating metastasis by establishing CTC-supportive emboli, and suggests points of intervention that may reduce the pro-metastatic effect of apoptotic cells.

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Section: Discussionsupporting

confidence: 84%

Apoptotic cells promote circulating tumor cell survival and metastasis

Hagan,

Snyder,

Headley

et al. 2024

Preprint

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“…Apoptotic cells influence the generation and localization of both of these proteins. By virtue of reorganization of their membrane phospholipids ( 83 , 84 ), apoptotic cells, and especially their shed microvesicles ( 85 ), are procoagulant, thereby providing a nidus for initiation and amplification of the coagulation cascade. In addition, exposure to apoptotic cells upregulates the expression by macrophages and endothelial cells of vascular endothelial growth factor (VEGF)-A, a factor that potently augments vascular permeability ( 73 , 86 , 87 ).…”

Section: Apoptotic Cells and The Hallmarks Of Cancermentioning

confidence: 99%

Exploitation of Apoptotic Regulation in Cancer

Ucker

Levine

2018

Front. Immunol.

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Within an organism, environmental stresses can trigger cell death, particularly apoptotic cell death. Apoptotic cells, themselves, are potent regulators of their cellular environment, involved primarily in effecting homeostatic control. Tumors, especially, exist in a dynamic balance of cell proliferation and cell death. This special feature of the tumorous microenvironment—namely, the prominence and persistence of cell death—necessarily entails a magnification of the extrinsic, postmortem effects of dead cells. In both normal and malignant tissues, apoptotic regulation is exerted through immune as well as non-immune mechanisms. Apoptotic cells suppress the repertoire of immune reactivities, both by attenuating innate (especially inflammatory) responses and by abrogating adaptive responses. In addition, apoptotic cells modulate multiple vital cell activities, including survival, proliferation (cell number), and growth (cell size). While the microenvironment of the tumor may contribute to apoptosis, the postmortem effects of apoptotic cells feature prominently in the reciprocal acclimatization between the tumor and its environment. In much the same way that pathogens evade the host’s defenses through exploitation of key aspects of innate and adaptive immunity, cancer cells subvert several normal homeostatic processes, in particular wound healing and organ regeneration, to transform and overtake their environment. In understanding this subversion, it is crucial to view a tumor not simply as a clone of malignant cells, but rather as a complex and highly organized structure in which there exists a multidirectional flow of information between the cancer cells themselves and the multiple other cell types and extracellular matrix components of which the tumor is comprised. Apoptotic cells, therefore, have the unfortunate consequence of facilitating tumorigenesis and tumor survival.

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The Pathogenetic Role of Apoptosis in Hypercoagulable States

Cited by 2 publications

References 85 publications

Apoptotic cells promote circulating tumor cell survival and metastasis

Apoptotic cells promote circulating tumor cell survival and metastasis

Exploitation of Apoptotic Regulation in Cancer

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