Inhibitory Effects of Megakaryocytes in Prostate Cancer Bone Metastasis
Abstract
The identification of the interaction between MKs and prostate cancer cells was the focus of this study. K562 (human megakaryocyte precursors), and primary MKs induced from mouse bone marrow hematopoietic precursor cells, potently suppressed prostate carcinoma PC-3 cells in co-culture. The inhibitory effects were specific to prostate carcinoma cells and were enhanced by direct cell-cell contact. Recombinant thrombopoietin (TPO) was used to expand MKs in the bone marrow and resulted in decreased prostate tumor skeletal lesion development after intra-cardiac tumor inoculation. Flow cytometry for propidium iodide (PI) and annexin V supported a pro-apoptotic role for K562 cells in limiting PC-3 cells. Gene expression analysis reduced mRNA levels for cyclin D1 while mRNA levels of apoptosis-associated speck-like protein containing a CARD (ASC) and death-associated protein kinase 1 (DAPK1) were increased in PC-3 cells after co-culture with K562 cells. These novel findings suggest a potent inhibitory role of MKs in prostate carcinoma cell growth in vivo and in vitro. This new interaction of metastatic tumors and hematopoietic cells, during tumor dissemination and colonization in bone, may ultimately lead to improved therapeutic interventions for prostate cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2010
- Accession Number
- ADA542172
Entities
People
- Laurie Mccauley
- Xin Li
Organizations
- University of Michigan