Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow

HSC homing, quiescence, and self-renewal depend on the bone marrow HSC niche. A large proportion of solid tumor metastases are bone metastases, known to usurp HSC homing pathways to establish footholds in the bone marrow. However, it is not clear whether tumors target the HSC niche during metastasis. Here we have shown in a mouse model of metastasis that human prostate cancer (PCa) cells directly compete with HSCs for occupancy of the mouse HSC niche. Importantly, increasing the niche size promoted metastasis, whereas decreasing the niche size compromised dissemination. Furthermore, disseminated PCa cells could be mobilized out of the niche and back into the circulation using HSC mobilization protocols.…

• UD
  U.S. Department of Defense
• PC
  Prostate Cancer Foundation
• UO
  University of Michigan

  Awards: P30 CA46592, 48109
• UO
  University of Connecticut
• NI
  National Institutes of Health

  Awards: CA69568, CA46592, P50 CA69568, CA093900, P30 CA46592
• CO
  College of Pharmacy, University of Michigan
• NC
  National Cancer Institute

  Awards: CA46592, CA093900, P30 CA46592, P50 CA69568