Estrogen enhances tumor growth and angiogenesis indirectly via mediation of bone marrow-derived cells as well as directly through stimulation of tumor and endothelial cells

Yingchen Zhuo, Xueqian Li, Qiaowei Zheng, Xingjun Fan, Wenbing Ma, Jingguo Chen, Xue Zhao, Peipei Zhao, Xuanlin Liu, Fengru Tang, Kai Cheng, Weiyi Feng

Research output: Contribution to journalArticle

Abstract

Estradiol (E2) is a prime culprit for enhancing the progression of female hormone.related cancers. Bone marrow.derived cells (BMDCs) have been found to play a pivotal role in tumor growth. Estrogen receptors (ERs) are also found on certain subtypes of BMDCs, in addition to endothelial cells (ECs) and certain tumor cells. However, the role of BMDCs in E2-induced tumor biology is still unclear. Thus, the effects of E2 on ER-negative 4T1 breast cancer growth, the mobilization and recruitment of BMDCs, and interactions among BMDCs, ECs, and 4T1 cells were investigated. The results showed that E2 potentiated 4T1 tumor growth and angiogenesis in mice subjected to sham operation, ovariectomy (OVX), or OVX and E2 replacement treatment. E2 supplementation in mice with OVX upregulated the transcription of stromal cell.derived factor-1 (SDF-1) mRNA in tumor tissues and enhanced the recruitment of BMDCs into tumor tissues in vivo. E2 deficiency significantly decreased proangiogenic CXCR4 + , β 3 + , Sca-1 + and CXCR4 + β 3 + BMDCs circulating in the peripheral blood. Cell-based system analyses showed that E2 augmented the transcription of β 3 mRNA in ECs, increased the adhesion of BMDCs to ECs. In addition, E2 enhanced the BMDC-induced EC proliferation and migration, the BMDC-induced 4T1 proliferation and the 4T1-stimulated EC proliferation in addition to enhancing the proliferation of tumor cells and the migration of ECs in vitro. Therefore, E2 enhanced the growth of breast tumors by stimulating tumor cells and ECs directly, as well as by increasing proangiogenic BMDC mobilization and recruitment leading to augmentation of the tumor and EC functions indirectly by cell proliferation assay. These findings reveal a separate mechanism via which E2 promotes the growth of female hormone-dependent tumors, which may be useful in explorations of new therapies for related cancers.

Original languageEnglish (US)
Pages (from-to)2147-2156
Number of pages10
JournalOncology Reports
Volume40
Issue number4
DOIs
StatePublished - Oct 1 2018

Fingerprint

Bone Marrow Cells
Estrogens
Endothelial Cells
Growth
Neoplasms
Cell Proliferation
Estrogen Receptors
Cell Movement
Breast Neoplasms
Messenger RNA
Second Primary Neoplasms
Ovariectomy
Stromal Cells
Systems Analysis
Cell Adhesion
Growth Hormone
Estradiol
Bone Marrow
Hormones

Keywords

  • Angiogenesis
  • Bone marrow cells
  • Breast carcinoma
  • Carcinogenesis
  • Estradiol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Estrogen enhances tumor growth and angiogenesis indirectly via mediation of bone marrow-derived cells as well as directly through stimulation of tumor and endothelial cells. / Zhuo, Yingchen; Li, Xueqian; Zheng, Qiaowei; Fan, Xingjun; Ma, Wenbing; Chen, Jingguo; Zhao, Xue; Zhao, Peipei; Liu, Xuanlin; Tang, Fengru; Cheng, Kai; Feng, Weiyi.

In: Oncology Reports, Vol. 40, No. 4, 01.10.2018, p. 2147-2156.

Research output: Contribution to journalArticle

Zhuo, Yingchen ; Li, Xueqian ; Zheng, Qiaowei ; Fan, Xingjun ; Ma, Wenbing ; Chen, Jingguo ; Zhao, Xue ; Zhao, Peipei ; Liu, Xuanlin ; Tang, Fengru ; Cheng, Kai ; Feng, Weiyi. / Estrogen enhances tumor growth and angiogenesis indirectly via mediation of bone marrow-derived cells as well as directly through stimulation of tumor and endothelial cells. In: Oncology Reports. 2018 ; Vol. 40, No. 4. pp. 2147-2156.
@article{059b6b6890cd480d86d09d21b986c953,
title = "Estrogen enhances tumor growth and angiogenesis indirectly via mediation of bone marrow-derived cells as well as directly through stimulation of tumor and endothelial cells",
abstract = "Estradiol (E2) is a prime culprit for enhancing the progression of female hormone.related cancers. Bone marrow.derived cells (BMDCs) have been found to play a pivotal role in tumor growth. Estrogen receptors (ERs) are also found on certain subtypes of BMDCs, in addition to endothelial cells (ECs) and certain tumor cells. However, the role of BMDCs in E2-induced tumor biology is still unclear. Thus, the effects of E2 on ER-negative 4T1 breast cancer growth, the mobilization and recruitment of BMDCs, and interactions among BMDCs, ECs, and 4T1 cells were investigated. The results showed that E2 potentiated 4T1 tumor growth and angiogenesis in mice subjected to sham operation, ovariectomy (OVX), or OVX and E2 replacement treatment. E2 supplementation in mice with OVX upregulated the transcription of stromal cell.derived factor-1 (SDF-1) mRNA in tumor tissues and enhanced the recruitment of BMDCs into tumor tissues in vivo. E2 deficiency significantly decreased proangiogenic CXCR4 + , β 3 + , Sca-1 + and CXCR4 + β 3 + BMDCs circulating in the peripheral blood. Cell-based system analyses showed that E2 augmented the transcription of β 3 mRNA in ECs, increased the adhesion of BMDCs to ECs. In addition, E2 enhanced the BMDC-induced EC proliferation and migration, the BMDC-induced 4T1 proliferation and the 4T1-stimulated EC proliferation in addition to enhancing the proliferation of tumor cells and the migration of ECs in vitro. Therefore, E2 enhanced the growth of breast tumors by stimulating tumor cells and ECs directly, as well as by increasing proangiogenic BMDC mobilization and recruitment leading to augmentation of the tumor and EC functions indirectly by cell proliferation assay. These findings reveal a separate mechanism via which E2 promotes the growth of female hormone-dependent tumors, which may be useful in explorations of new therapies for related cancers.",
keywords = "Angiogenesis, Bone marrow cells, Breast carcinoma, Carcinogenesis, Estradiol",
author = "Yingchen Zhuo and Xueqian Li and Qiaowei Zheng and Xingjun Fan and Wenbing Ma and Jingguo Chen and Xue Zhao and Peipei Zhao and Xuanlin Liu and Fengru Tang and Kai Cheng and Weiyi Feng",
year = "2018",
month = "10",
day = "1",
doi = "10.3892/or.2018.6631",
language = "English (US)",
volume = "40",
pages = "2147--2156",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "4",

}

TY - JOUR

T1 - Estrogen enhances tumor growth and angiogenesis indirectly via mediation of bone marrow-derived cells as well as directly through stimulation of tumor and endothelial cells

AU - Zhuo, Yingchen

AU - Li, Xueqian

AU - Zheng, Qiaowei

AU - Fan, Xingjun

AU - Ma, Wenbing

AU - Chen, Jingguo

AU - Zhao, Xue

AU - Zhao, Peipei

AU - Liu, Xuanlin

AU - Tang, Fengru

AU - Cheng, Kai

AU - Feng, Weiyi

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Estradiol (E2) is a prime culprit for enhancing the progression of female hormone.related cancers. Bone marrow.derived cells (BMDCs) have been found to play a pivotal role in tumor growth. Estrogen receptors (ERs) are also found on certain subtypes of BMDCs, in addition to endothelial cells (ECs) and certain tumor cells. However, the role of BMDCs in E2-induced tumor biology is still unclear. Thus, the effects of E2 on ER-negative 4T1 breast cancer growth, the mobilization and recruitment of BMDCs, and interactions among BMDCs, ECs, and 4T1 cells were investigated. The results showed that E2 potentiated 4T1 tumor growth and angiogenesis in mice subjected to sham operation, ovariectomy (OVX), or OVX and E2 replacement treatment. E2 supplementation in mice with OVX upregulated the transcription of stromal cell.derived factor-1 (SDF-1) mRNA in tumor tissues and enhanced the recruitment of BMDCs into tumor tissues in vivo. E2 deficiency significantly decreased proangiogenic CXCR4 + , β 3 + , Sca-1 + and CXCR4 + β 3 + BMDCs circulating in the peripheral blood. Cell-based system analyses showed that E2 augmented the transcription of β 3 mRNA in ECs, increased the adhesion of BMDCs to ECs. In addition, E2 enhanced the BMDC-induced EC proliferation and migration, the BMDC-induced 4T1 proliferation and the 4T1-stimulated EC proliferation in addition to enhancing the proliferation of tumor cells and the migration of ECs in vitro. Therefore, E2 enhanced the growth of breast tumors by stimulating tumor cells and ECs directly, as well as by increasing proangiogenic BMDC mobilization and recruitment leading to augmentation of the tumor and EC functions indirectly by cell proliferation assay. These findings reveal a separate mechanism via which E2 promotes the growth of female hormone-dependent tumors, which may be useful in explorations of new therapies for related cancers.

AB - Estradiol (E2) is a prime culprit for enhancing the progression of female hormone.related cancers. Bone marrow.derived cells (BMDCs) have been found to play a pivotal role in tumor growth. Estrogen receptors (ERs) are also found on certain subtypes of BMDCs, in addition to endothelial cells (ECs) and certain tumor cells. However, the role of BMDCs in E2-induced tumor biology is still unclear. Thus, the effects of E2 on ER-negative 4T1 breast cancer growth, the mobilization and recruitment of BMDCs, and interactions among BMDCs, ECs, and 4T1 cells were investigated. The results showed that E2 potentiated 4T1 tumor growth and angiogenesis in mice subjected to sham operation, ovariectomy (OVX), or OVX and E2 replacement treatment. E2 supplementation in mice with OVX upregulated the transcription of stromal cell.derived factor-1 (SDF-1) mRNA in tumor tissues and enhanced the recruitment of BMDCs into tumor tissues in vivo. E2 deficiency significantly decreased proangiogenic CXCR4 + , β 3 + , Sca-1 + and CXCR4 + β 3 + BMDCs circulating in the peripheral blood. Cell-based system analyses showed that E2 augmented the transcription of β 3 mRNA in ECs, increased the adhesion of BMDCs to ECs. In addition, E2 enhanced the BMDC-induced EC proliferation and migration, the BMDC-induced 4T1 proliferation and the 4T1-stimulated EC proliferation in addition to enhancing the proliferation of tumor cells and the migration of ECs in vitro. Therefore, E2 enhanced the growth of breast tumors by stimulating tumor cells and ECs directly, as well as by increasing proangiogenic BMDC mobilization and recruitment leading to augmentation of the tumor and EC functions indirectly by cell proliferation assay. These findings reveal a separate mechanism via which E2 promotes the growth of female hormone-dependent tumors, which may be useful in explorations of new therapies for related cancers.

KW - Angiogenesis

KW - Bone marrow cells

KW - Breast carcinoma

KW - Carcinogenesis

KW - Estradiol

UR - http://www.scopus.com/inward/record.url?scp=85051545290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051545290&partnerID=8YFLogxK

U2 - 10.3892/or.2018.6631

DO - 10.3892/or.2018.6631

M3 - Article

VL - 40

SP - 2147

EP - 2156

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 4

ER -