Osteolytic cancer cells induce vascular/axon guidance processes in the bone/bone marrow stroma

Janine Hensel, Antoinette Wetterwald, Ramzi Temanni, Irene Keller, Carsten Riether, Gabri van der Pluijm, Marco G. Cecchini, George N. Thalmann

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1 Citation (Scopus)

Abstract

Prostate and breast cancers frequently metastasize to bone. The physiological bone homeostasis is perturbed once cancer cells proliferate at the bone metastatic site. Tumors are complex structures consisting of cancer cells and numerous stroma cells. In this study, we show that osteolytic cancer cells (PC-3 and MDA-MB231) induce transcriptome changes in the bone/bone marrow microenvironment (stroma). This stroma transcriptome differs from the previously reported stroma transcriptome of osteoinductive cancer cells (VCaP). While the biological process "angiogenesis/ vasculogenesis" is enriched in both transcriptomes, the "vascular/axon guidance" process is a unique process that characterizes the osteolytic stroma. In osteolytic bone metastasis, angiogenesis is denoted by vessel morphology and marker expression specific for arteries/arterioles. Interestingly, intra-tumoral neuritelike structures were in proximity to arteries. Additionally, we found that increased numbers of mesenchymal stem cells and vascular smooth muscle cells, expressing osteolytic cytokines and inhibitors of bone formation, contribute to the osteolytic bone phenotype. Osteoinductive and osteolytic cancer cells induce different types of vessels, representing functionally different hematopoietic stem cell niches. This finding suggests different growth requirements of osteolytic and osteoinductive cancer cells and the need for a differential anti-angiogenic strategy to inhibit tumor growth in osteolytic and osteoblastic bone metastasis.

Original languageEnglish
Pages (from-to)28877-28896
Number of pages20
JournalOncotarget
Volume9
Issue number48
DOIs
Publication statusPublished - 22 Jun 2018

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Keywords

  • Angiogenesis
  • Axon guidance
  • Osteolytic bone metastasis
  • Prostate and breast cancer
  • Stroma

ASJC Scopus subject areas

  • Oncology

Cite this

Hensel, J., Wetterwald, A., Temanni, R., Keller, I., Riether, C., Pluijm, G. V. D., Cecchini, M. G., & Thalmann, G. N. (2018). Osteolytic cancer cells induce vascular/axon guidance processes in the bone/bone marrow stroma. Oncotarget, 9(48), 28877-28896. https://doi.org/10.18632/oncotarget.25608