Role of Megakaryocytes in Breast Cancer Metastasis to Bone

Little is known about how megakaryocytes may affect metastasis beyond serving as a source of platelets. In this study, we explored the functional implications of megakaryocyte accumulation in the femurs of mice after injection of metastatic or non-metastatic breast cancer cells in 4T1.2 BALB/cJ and...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2017-04, Vol.77 (8), p.1942-1954
Hauptverfasser: Jackson, 3rd, Walter, Sosnoski, Donna M, Ohanessian, Sara E, Chandler, Paige, Mobley, Adam, Meisel, Kacey D, Mastro, Andrea M
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container_end_page 1954
container_issue 8
container_start_page 1942
container_title Cancer research (Chicago, Ill.)
container_volume 77
creator Jackson, 3rd, Walter
Sosnoski, Donna M
Ohanessian, Sara E
Chandler, Paige
Mobley, Adam
Meisel, Kacey D
Mastro, Andrea M
description Little is known about how megakaryocytes may affect metastasis beyond serving as a source of platelets. In this study, we explored the functional implications of megakaryocyte accumulation in the femurs of mice after injection of metastatic or non-metastatic breast cancer cells in 4T1.2 BALB/cJ and MDA-MB-231 nude mouse models. At bone metastatic sites, but not primary growth sites, tumor growth was associated with increased megakaryopoiesis in both model systems. In the orthotopic BALB/cJ model, extramedullary hematopoiesis occurred in the spleen, resulting in a four-fold increase in megakaryocytes. In support of the hypothesis that reducing megakaryocytes may reduce metastasis, we found that thrombopoietin-deficient mice exhibited a 90% relative decrease in megakaryocytes, yet they developed more aggressive metastasis than wild-type hosts. In human clinical specimens, we observed an increase in megakaryocytes in the bone marrow of 6/8 patients with metastatic breast cancer compared with age- and gender-matched controls. Taken together, our results suggested that an increase in megakaryocytes occurring in response to metastatic cells entering the bone marrow confers some measure of protection against metastasis, challenging present views on the role of megakaryocytes in this setting. .
doi_str_mv 10.1158/0008-5472.can-16-1084
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research
subjects 3T3 Cells
Animal models
Animals
Bone cancer
Bone marrow
Bone Neoplasms - secondary
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - pathology
Cell Line, Tumor
Female
Hematopoiesis
Humans
Mammary Neoplasms, Experimental - blood
Mammary Neoplasms, Experimental - pathology
Megakaryocytes
Megakaryocytes - pathology
Metastases
Metastasis
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Osteoblasts - pathology
Platelets
Spleen
Thrombopoietin
title Role of Megakaryocytes in Breast Cancer Metastasis to Bone
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