Adipocytes enhance the proliferation of human leiomyoma cells via TNF-α proinflammatory cytokine

Sangeeta Nair, Ayman Al-Hendy

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objective: Obesity is a well-documented risk factor for uterine leiomyoma with a major impact on women health and health care system of the nation. Obesity is associated with increased secretion of adipokines that significantly influence growth and proliferation of tumor stroma and malignant cells. Adipokines, such as tumor necrosis factor α (TNF-α), are produced in the adipose tissue with concomitant expression in other organs and tissues. Increased and sustained cytokine production is associated with alterations in cell growth and differentiation. We, therefore, explored the influence of human adipocytes (SW872 cells)-mediated biological humoral factors on human uterine leiomyoma (HuLM) cells. Methods: We measured cell proliferation and expression of cell-proliferating proteins (proliferating cell nuclear antigen [PCNA], cyclin D1, and B-cell lymphoma 2 [BCL-2]) in human leiomyoma cells cocultured with SW872 cells. SW872-conditioned media was neutralized for TNF-α and proliferation of HuLM cells was observed along with antiapoptotic marker, BCL-2, using Western immunoblot. Results: We found that both SW872-conditioned media and coculture with SW872 cells increased HuLM cell proliferation significantly (P <.05). We determined that this effect was associated with the upregulation of specific markers for proliferation, such as PCNA, cyclin D1, and BCL-2 (P <.05). Furthermore, the addition of neutralizing antibodies, anti- TNF-α, to SW872-conditioned media reversed the proliferation of leiomyoma cells and induced apoptosis as indicated by the reduced expression of antiapoptotic marker BCL-2. Conclusions: SW872 cells secrete TNF-α, which is associated with a proliferative gene profile in HuLM cells and may play a role in initiation and/or progression of uterine leiomyoma.

Original languageEnglish (US)
Pages (from-to)1186-1192
Number of pages7
JournalReproductive Sciences
Volume18
Issue number12
DOIs
StatePublished - Dec 1 2011

Fingerprint

Leiomyoma
Adipocytes
Tumor Necrosis Factor-alpha
Cytokines
B-Cell Lymphoma
Conditioned Culture Medium
Cyclin B
Adipokines
Cyclin D1
Cell Proliferation
Proliferating Cell Nuclear Antigen
Obesity
Biological Factors
Women's Health
Growth
Coculture Techniques
Neutralizing Antibodies
Adipose Tissue
Cell Differentiation
Up-Regulation

Keywords

  • adipokines
  • coculture
  • obesity
  • uterine leiomyoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Adipocytes enhance the proliferation of human leiomyoma cells via TNF-α proinflammatory cytokine. / Nair, Sangeeta; Al-Hendy, Ayman.

In: Reproductive Sciences, Vol. 18, No. 12, 01.12.2011, p. 1186-1192.

Research output: Contribution to journalArticle

Nair, Sangeeta ; Al-Hendy, Ayman. / Adipocytes enhance the proliferation of human leiomyoma cells via TNF-α proinflammatory cytokine. In: Reproductive Sciences. 2011 ; Vol. 18, No. 12. pp. 1186-1192.
@article{d0d16b9360c447e29d656336cd762bc0,
title = "Adipocytes enhance the proliferation of human leiomyoma cells via TNF-α proinflammatory cytokine",
abstract = "Objective: Obesity is a well-documented risk factor for uterine leiomyoma with a major impact on women health and health care system of the nation. Obesity is associated with increased secretion of adipokines that significantly influence growth and proliferation of tumor stroma and malignant cells. Adipokines, such as tumor necrosis factor α (TNF-α), are produced in the adipose tissue with concomitant expression in other organs and tissues. Increased and sustained cytokine production is associated with alterations in cell growth and differentiation. We, therefore, explored the influence of human adipocytes (SW872 cells)-mediated biological humoral factors on human uterine leiomyoma (HuLM) cells. Methods: We measured cell proliferation and expression of cell-proliferating proteins (proliferating cell nuclear antigen [PCNA], cyclin D1, and B-cell lymphoma 2 [BCL-2]) in human leiomyoma cells cocultured with SW872 cells. SW872-conditioned media was neutralized for TNF-α and proliferation of HuLM cells was observed along with antiapoptotic marker, BCL-2, using Western immunoblot. Results: We found that both SW872-conditioned media and coculture with SW872 cells increased HuLM cell proliferation significantly (P <.05). We determined that this effect was associated with the upregulation of specific markers for proliferation, such as PCNA, cyclin D1, and BCL-2 (P <.05). Furthermore, the addition of neutralizing antibodies, anti- TNF-α, to SW872-conditioned media reversed the proliferation of leiomyoma cells and induced apoptosis as indicated by the reduced expression of antiapoptotic marker BCL-2. Conclusions: SW872 cells secrete TNF-α, which is associated with a proliferative gene profile in HuLM cells and may play a role in initiation and/or progression of uterine leiomyoma.",
keywords = "adipokines, coculture, obesity, uterine leiomyoma",
author = "Sangeeta Nair and Ayman Al-Hendy",
year = "2011",
month = "12",
day = "1",
doi = "10.1177/1933719111408111",
language = "English (US)",
volume = "18",
pages = "1186--1192",
journal = "Reproductive Sciences",
issn = "1933-7191",
publisher = "SAGE Publications Inc.",
number = "12",

}

TY - JOUR

T1 - Adipocytes enhance the proliferation of human leiomyoma cells via TNF-α proinflammatory cytokine

AU - Nair, Sangeeta

AU - Al-Hendy, Ayman

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Objective: Obesity is a well-documented risk factor for uterine leiomyoma with a major impact on women health and health care system of the nation. Obesity is associated with increased secretion of adipokines that significantly influence growth and proliferation of tumor stroma and malignant cells. Adipokines, such as tumor necrosis factor α (TNF-α), are produced in the adipose tissue with concomitant expression in other organs and tissues. Increased and sustained cytokine production is associated with alterations in cell growth and differentiation. We, therefore, explored the influence of human adipocytes (SW872 cells)-mediated biological humoral factors on human uterine leiomyoma (HuLM) cells. Methods: We measured cell proliferation and expression of cell-proliferating proteins (proliferating cell nuclear antigen [PCNA], cyclin D1, and B-cell lymphoma 2 [BCL-2]) in human leiomyoma cells cocultured with SW872 cells. SW872-conditioned media was neutralized for TNF-α and proliferation of HuLM cells was observed along with antiapoptotic marker, BCL-2, using Western immunoblot. Results: We found that both SW872-conditioned media and coculture with SW872 cells increased HuLM cell proliferation significantly (P <.05). We determined that this effect was associated with the upregulation of specific markers for proliferation, such as PCNA, cyclin D1, and BCL-2 (P <.05). Furthermore, the addition of neutralizing antibodies, anti- TNF-α, to SW872-conditioned media reversed the proliferation of leiomyoma cells and induced apoptosis as indicated by the reduced expression of antiapoptotic marker BCL-2. Conclusions: SW872 cells secrete TNF-α, which is associated with a proliferative gene profile in HuLM cells and may play a role in initiation and/or progression of uterine leiomyoma.

AB - Objective: Obesity is a well-documented risk factor for uterine leiomyoma with a major impact on women health and health care system of the nation. Obesity is associated with increased secretion of adipokines that significantly influence growth and proliferation of tumor stroma and malignant cells. Adipokines, such as tumor necrosis factor α (TNF-α), are produced in the adipose tissue with concomitant expression in other organs and tissues. Increased and sustained cytokine production is associated with alterations in cell growth and differentiation. We, therefore, explored the influence of human adipocytes (SW872 cells)-mediated biological humoral factors on human uterine leiomyoma (HuLM) cells. Methods: We measured cell proliferation and expression of cell-proliferating proteins (proliferating cell nuclear antigen [PCNA], cyclin D1, and B-cell lymphoma 2 [BCL-2]) in human leiomyoma cells cocultured with SW872 cells. SW872-conditioned media was neutralized for TNF-α and proliferation of HuLM cells was observed along with antiapoptotic marker, BCL-2, using Western immunoblot. Results: We found that both SW872-conditioned media and coculture with SW872 cells increased HuLM cell proliferation significantly (P <.05). We determined that this effect was associated with the upregulation of specific markers for proliferation, such as PCNA, cyclin D1, and BCL-2 (P <.05). Furthermore, the addition of neutralizing antibodies, anti- TNF-α, to SW872-conditioned media reversed the proliferation of leiomyoma cells and induced apoptosis as indicated by the reduced expression of antiapoptotic marker BCL-2. Conclusions: SW872 cells secrete TNF-α, which is associated with a proliferative gene profile in HuLM cells and may play a role in initiation and/or progression of uterine leiomyoma.

KW - adipokines

KW - coculture

KW - obesity

KW - uterine leiomyoma

UR - http://www.scopus.com/inward/record.url?scp=81555208672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81555208672&partnerID=8YFLogxK

U2 - 10.1177/1933719111408111

DO - 10.1177/1933719111408111

M3 - Article

VL - 18

SP - 1186

EP - 1192

JO - Reproductive Sciences

JF - Reproductive Sciences

SN - 1933-7191

IS - 12

ER -