Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy

Kentaro Nobutani, Yohei Shimono, Kiyohito Mizutani, Yuki Ueda, Toshihiro Suzuki, Midori Kitayama, Akihiro Minami, Kenji Momose, Kohta Miyawaki, Koichi Akashi, Takeshi Azuma, Yoshimi Takai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Our understanding of the mechanism of cancer dormancy is emerging, but the underlying mechanisms are not fully understood. Here we analyzed mouse xenograft tumors derived from human breast cancer tissue and the human breast cancer cell line MDA-MB-231 to identify the molecules associated with cancer dormancy. In immunohistological examination using the proliferation marker Ki-67, the tumors included both proliferating and dormant cancer cells, but the number of dormant cells was remarkably increased when they metastasized to the lung. In the gene expression analysis of the orthotopic cancer cells by a single-cell multiplex real-time quantitative reverse transcription PCR followed by flow cytometric analysis, restrained cellular proliferation was associated with downregulation of the chemokine receptor CXCR4. In the immunohistological and flow cytometric analyses, the expression level of CXCR4 in the metastasized cancer cells was decreased compared with that in the cancer cells in orthotopic tumors, although the expression level of the CXCR4 ligand CXCL12 was not reduced in the lung. In addition, the proliferation of the metastasized cancer cells was further decreased by the CXCR4 antagonist administration. In the ex vivo culture of the metastasized cancer cells, the expression level of CXCR4 was increased, and in the xenotransplantation of ex vivo cultured cancer cells, the expression level of CXCR4 was again decreased in the metastasized cancer cells in the lung. These findings indicate that CXCR4 is downregulated in metastasized breast cancer cells and implicated in their dormancy.

Original languageEnglish
Article number0130032
JournalPloS one
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 17 2015

Fingerprint

breast neoplasms
dormancy
Down-Regulation
Cells
Breast Neoplasms
Neoplasms
neoplasms
Tumors
lungs
neoplasm cells
Lung
xenotransplantation
Chemokine Receptors
Transcription
Cell culture
Heterografts
Gene expression
Heterologous Transplantation
cultured cells
antagonists

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Nobutani, K., Shimono, Y., Mizutani, K., Ueda, Y., Suzuki, T., Kitayama, M., ... Takai, Y. (2015). Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy. PloS one, 10(6), [0130032]. https://doi.org/10.1371/journal.pone.0130032

Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy. / Nobutani, Kentaro; Shimono, Yohei; Mizutani, Kiyohito; Ueda, Yuki; Suzuki, Toshihiro; Kitayama, Midori; Minami, Akihiro; Momose, Kenji; Miyawaki, Kohta; Akashi, Koichi; Azuma, Takeshi; Takai, Yoshimi.

In: PloS one, Vol. 10, No. 6, 0130032, 17.06.2015.

Research output: Contribution to journalArticle

Nobutani, K, Shimono, Y, Mizutani, K, Ueda, Y, Suzuki, T, Kitayama, M, Minami, A, Momose, K, Miyawaki, K, Akashi, K, Azuma, T & Takai, Y 2015, 'Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy', PloS one, vol. 10, no. 6, 0130032. https://doi.org/10.1371/journal.pone.0130032
Nobutani K, Shimono Y, Mizutani K, Ueda Y, Suzuki T, Kitayama M et al. Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy. PloS one. 2015 Jun 17;10(6). 0130032. https://doi.org/10.1371/journal.pone.0130032
Nobutani, Kentaro ; Shimono, Yohei ; Mizutani, Kiyohito ; Ueda, Yuki ; Suzuki, Toshihiro ; Kitayama, Midori ; Minami, Akihiro ; Momose, Kenji ; Miyawaki, Kohta ; Akashi, Koichi ; Azuma, Takeshi ; Takai, Yoshimi. / Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy. In: PloS one. 2015 ; Vol. 10, No. 6.
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