Estrous Cycle Modulates Ovarian Carcinoma Growth

Guillermo N ARMAIZ-PENA; Lingegowda S MANGALA; Anil K SOOD; WhitneyA SPANNUTH; Yvonne G LIN; Nicholas B JENNINGS; Alpa M NICK; Robert R LANGLEY; Rosemarie SCHMANDT; Susan K LUTGENDORF; Steven W COLE

doi:10.1158/1078-0432.CCR-08-2525

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Estrous Cycle Modulates Ovarian Carcinoma Growth

Journal article

Open access

Peer reviewed

Estrous Cycle Modulates Ovarian Carcinoma Growth

Guillermo N ARMAIZ-PENA, Lingegowda S MANGALA, Anil K SOOD, WhitneyA SPANNUTH, Yvonne G LIN, Nicholas B JENNINGS, Alpa M NICK, Robert R LANGLEY, Rosemarie SCHMANDT, Susan K LUTGENDORF, …

Clinical cancer research, Vol.15(9), pp.2971-2978

2009

DOI: 10.1158/1078-0432.CCR-08-2525

PMCID: PMC2743312

PMID: 19383821

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Abstract

Purpose: The effects of reproductive hormones on ovarian cancer growth are not well understood. Here, we examined the effects of estrous cycle variation and specific reproductive hormones on ovarian cancer growth. Experimental design: We investigated the role of reproductive hormones in ovarian cancer growth using both in vivo and in vitro models of tumor growth. Results: In vivo experiments using the HeyA8 and SKOV3ip1 ovarian cancer models showed that tumor cell inoculation during proestrus significantly increased tumor burden (251-273%) compared with injection during the estrus phase. Treatment of ovariectomized mice with 17beta-estradiol resulted in a 404% to 483% increase in tumor growth compared with controls. Progestins had no significant effect, but did block estrogen-stimulated tumor growth. Tumors collected from mice sacrificed during proestrus showed increased levels of vascular endothelial growth factor (VEGF) and microvessel density compared with mice injected during estrus. HeyA8, SKOV3ip1, and mouse endothelial (MOEC) cells expressed estrogen receptor alpha and beta and progesterone receptor at the protein and mRNA levels, whereas 2774 ovarian cancer cells were estrogen receptor-negative. In vitro assays showed that 17beta-estradiol significantly increased ovarian cancer cell adhesion to collagen in estrogen receptor-positive, but not in estrogen receptor-negative cells. Additionally, 17beta-estradiol increased the migratory potential of MOEC cells, which was abrogated by the mitogen-activated protein kinase (MAPK) inhibitor, PD 09859. Treatment with 17beta-estradiol activated MAPK in MOEC cells, but not in HeyA8 or SKOV3ip1 cells. Conclusion: Our data suggest that estrogen may promote in vivo ovarian cancer growth, both directly and indirectly, by making the tumor microenvironment more conducive for cancer growth.

Antineoplastic Agents

Tumors

Gynecology. Andrology. Obstetrics

Pharmacology. Drug treatments

Biological and medical sciences

Medical sciences

Female genital diseases

Details

Title: Subtitle: Estrous Cycle Modulates Ovarian Carcinoma Growth
Creators: Guillermo N ARMAIZ-PENA - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
Lingegowda S MANGALA - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
Anil K SOOD - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
WhitneyA SPANNUTH - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
Yvonne G LIN - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
Nicholas B JENNINGS - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
Alpa M NICK - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
Robert R LANGLEY - Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, United States
Rosemarie SCHMANDT - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, United States
Susan K LUTGENDORF - Department of Psychology, University of lowa, Iowa City, Iowa, United States
Steven W COLE - Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles School of Medicine, Los Angeles, California, United States
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.15(9), pp.2971-2978
DOI: 10.1158/1078-0432.CCR-08-2525
PMID: 19383821
PMCID: PMC2743312
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Publisher: American Association for Cancer Research; Philadelphia, PA
Language: English
Date published: 2009
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
Record Identifier: 9984065775602771

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