Trabectedin Reduces Skeletal Prostate Cancer Tumor Size in Association with Effects on M2 Macrophages and Efferocytosis

Research output: Contribution to journalResearch articleContributedpeer-review


  • J. D. Jones - , University of Michigan, Ann Arbor (Author)
  • B. P. Sinder - , University of Michigan, Ann Arbor (Author)
  • D. Paige - , University of Michigan, Ann Arbor (Author)
  • A. J. Koh - , University of Michigan, Ann Arbor (Author)
  • S. Thiele - , Department of internal Medicine 3 (Author)
  • Y. Shiozawa - , University of Michigan, Ann Arbor, Wake Forest University (Author)
  • L. C. Hofbauer - , Department of internal Medicine 3, German Cancer Research Center (DKFZ) (Author)
  • S. Daignault - , University of Michigan, Ann Arbor (Author)
  • H. Roca - , University of Michigan, Ann Arbor (Author)
  • L. K. McCauley - , University of Michigan, Ann Arbor (Author)


Macrophages play a dual role in regulating tumor progression. They can either reduce tumor growth by secreting antitumorigenic factors or promote tumor progression by secreting a variety of soluble factors. The purpose of this study was to define the monocyte/macrophage population prevalent in skeletal tumors, explore a mechanism employed in supporting prostate cancer (PCa) skeletal metastasis, and examine a novel therapeutic target. Phagocytic CD68+ cells were found to correlate with Gleason score in human PCa samples, and M2-like macrophages (F4/80+CD206+) were identified in PCa bone resident tumors in mice. Induced M2-like macrophages in vitro were more proficient at phagocytosis (efferocytosis) of apoptotic tumor cells than M1-like macrophages. Moreover, soluble factors released from efferocytic versus nonefferocytic macrophages increased PC-3 prostate cancer cell numbers in vitro. Trabectedin exposure reduced M2-like (F4/80+CD206+) macrophages in vivo. Trabectedin administration after PC-3 cell intracardiac inoculation reduced skeletal metastatic tumor growth. Preventative pretreatment with trabectedin 7 days prior to PC-3 cell injection resulted in reduced M2-like macrophages in the marrow and reduced skeletal tumor size. Together, these findings suggest that M2-like monocytes and macrophages promote PCa skeletal metastasis and that trabectedin represents a candidate therapeutic target.


Original languageEnglish
Pages (from-to)172-184
Number of pages13
JournalNeoplasia (United States)
Issue number2
Publication statusPublished - Feb 2019

External IDs

PubMed 30591422
ORCID /0000-0002-8691-8423/work/142236115
ORCID /0000-0001-9345-026X/work/150328897


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