Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis

Xin Li, Amy J. Koh, Zhengyan Wang, Fabiana N. Soki, Serk In Park, Kenneth J. Pienta, Laurie K. McCauley

Research output: Contribution to journalArticle

Abstract

Prostate cancer cells commonly spread through the circulation, but few successfully generate metastatic foci in bone. Osteoclastic cellular activity has been proposed as an initiating event for skeletal metastasis. Megakaryocytes (MKs) inhibit osteoclastogenesis, which could have an impact on tumor establishment in bone. Given the location of mature MKs at vascular sinusoids, they may be the first cells to physically encounter cancer cells as they enter the bone marrow. Identification of the interaction between MKs and prostate cancer cells was the focus of this study. K562 (human MK precursors) and primary MKs derived from mouse bone marrow hematopoietic precursor cells potently suppressed prostate carcinoma PC-3 cells in coculture. The inhibitory effects were specific to prostate carcinoma cells and were enhanced by direct cell-cell contact. Flow cytometry for propidium iodide (PI) and annexin V supported a proapoptotic role for K562 cells in limiting PC-3 cells. Gene expression analysis revealed reduced mRNA levels for cyclin D1, whereas mRNA levels of apoptosis-associated specklike protein containing a CARD (ASC) and death-associated protein kinase 1 (DAPK1) were increased in PC-3 cells after coculture with K562 cells. Recombinant thrombopoietin (TPO) was used to expand MKs in the marrow and resulted in decreased skeletal lesion development after intracardiac tumor inoculation. These novel findings suggest a potent inhibitory role of MKs in prostate carcinoma cell growth in vitro and in vivo. This new finding, of an interaction of metastatic tumors and hematopoietic cells during tumor colonization in bone, ultimately will lead to improved therapeutic interventions for prostate cancer patients.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalJournal of Bone and Mineral Research
Volume26
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Prostatic Neoplasms
Neoplasm Metastasis
Megakaryocytes
Prostate
K562 Cells
Bone Marrow
Neoplasms
Coculture Techniques
Carcinoma
Bone and Bones
Death-Associated Protein Kinases
Thrombopoietin
Messenger RNA
Propidium
Annexin A5
Cyclin D1
Osteogenesis
Blood Vessels
Flow Cytometry
Apoptosis

Keywords

  • APOPTOSIS
  • MEGAKARYOCYTES
  • PROSTATE CARCINOMA
  • SKELETAL METASTASIS

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Li, X., Koh, A. J., Wang, Z., Soki, F. N., Park, S. I., Pienta, K. J., & McCauley, L. K. (2011). Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis. Journal of Bone and Mineral Research, 26(1), 125-134. https://doi.org/10.1002/jbmr.204

Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis. / Li, Xin; Koh, Amy J.; Wang, Zhengyan; Soki, Fabiana N.; Park, Serk In; Pienta, Kenneth J.; McCauley, Laurie K.

In: Journal of Bone and Mineral Research, Vol. 26, No. 1, 01.2011, p. 125-134.

Research output: Contribution to journalArticle

Li, X, Koh, AJ, Wang, Z, Soki, FN, Park, SI, Pienta, KJ & McCauley, LK 2011, 'Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis', Journal of Bone and Mineral Research, vol. 26, no. 1, pp. 125-134. https://doi.org/10.1002/jbmr.204
Li, Xin ; Koh, Amy J. ; Wang, Zhengyan ; Soki, Fabiana N. ; Park, Serk In ; Pienta, Kenneth J. ; McCauley, Laurie K. / Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis. In: Journal of Bone and Mineral Research. 2011 ; Vol. 26, No. 1. pp. 125-134.
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