4.1 Article

N-cadherin in osteolineage cells modulates stromal support of tumor growth

期刊

JOURNAL OF BONE ONCOLOGY
卷 28, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.jbo.2021.100356

关键词

N-cadherin; Bone-tumor cell interactions; Tumor microenvironment; Transcriptomics

类别

资金

  1. National Institutes of Health [R01 CA243383, P01 CA100730, CA154737, CA097250]
  2. Barnes-Jewish Hospital Foundation
  3. Siteman Cancer Center Investment Program
  4. Washington University Institute for Clinical and Translational Sciences Just-In-Time Program - NIH CTSA [UL1 TR002345]
  5. St. Louis Men's Group Against Cancer
  6. Core Center for Musculoskeletal Biology and Medicine [P30 AR057235]
  7. Genome Technology Access Center [P30 CA91842]
  8. National Center for Research Resources, a component of the NIH [UL1 TR002345]
  9. NIH Roadmap for Medical Research

向作者/读者索取更多资源

Expression of the cell-cell adhesion molecule N-cadherin is associated with aggressive cancers, but its role in bone metastasis and extra-skeletal tumor formation is unclear.
Tumor growth and metastases are dependent on interactions between cancer cells and the local environment. Expression of the cell-cell adhesion molecule N-cadherin (Ncad) is associated with highly aggressive cancers, and its expression by osteogenic cells has been proposed to provide a molecular dock for disseminated tumor cells to establish in pre-metastatic niches within the bone. To test this biologic model, we conditionally deleted the Ncad gene (Cdh2) in osteolineage cells using Osx-cre (cKO). Contrary to expectations, the metastatic breast cancer cell line PyMT-BO1 was able to form tumors in bone and to induce osteolysis in cKO as well as in control mice. Despite absence of Ncad, bone marrow stromal cells isolated from cKO mice were able to engage in direct cell-cell interactions with tumor cells expressing either N-or E-cadherin. However, subcutaneous PyMT-BO1 and B16F10 tumors grew larger in cKO relative to control littermates. Cell tracking experiments using the Ai9 reporter revealed the presence of Osx+ and Ncad+ cells in the stroma of extra-skeletal tumors and in a small population of lung cells. Gene expression analysis by RNAseq of Osx+ cells isolated from extra-skeletal tumors revealed alterations of pro-tumorigenic signaling pathways in cKO cells relative to control Osx+ cells. Thus, Ncad in Osx+ cells is not necessary for the establishment of bone metastases, but in extra-skeletal tumors it regulates pro-tumorigenic support by the microenvironment. (c) 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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