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

Hensel, Janine; Wetterwald, Antoinette; Temanni, Ramzi; Keller, Irene; Riether, Carsten; van der Pluijm, Gabri; Cecchini, Marco G; Thalmann, George N. (2018). Osteolytic cancer cells induce vascular/axon guidance processes in the bone/bone marrow stroma. OncoTarget, 9(48), pp. 28877-28896. Impact Journals LLC 10.18632/oncotarget.25608

[img]
Preview
Text
Tha_oseolytic cancer cells induce vascular axon guidance pocesses in the bone bone marrow stroma_08012019.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (9MB) | Preview

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 neurite-like 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Riether, Carsten and Thalmann, George

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Jeannine Wiemann

Date Deposited:

22 Jan 2019 12:25

Last Modified:

01 Nov 2019 02:22

Publisher DOI:

10.18632/oncotarget.25608

PubMed ID:

29988965

Uncontrolled Keywords:

angiogenesis axon guidance osteolytic bone metastasis prostate and breast cancer stroma

BORIS DOI:

10.7892/boris.123417

URI:

https://boris.unibe.ch/id/eprint/123417

Actions (login required)

Edit item Edit item
Provide Feedback