Relative overexpression of collagen type I and collagen type III messenger ribonucleic acids by uterine leiomyomas during the proliferative phase of the menstrual cycle
EA Stewart, AJ Friedman, K Peck and RA Nowak
Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts.
Uterine leiomyomas contain abundant quantities of extracellular matrix
(ECM). We characterized the localization of three ECM proteins, collagen
type I, collagen type III, and fibronectin, in leiomyomas and adjacent
normal myometrium. We further examined the expression of messenger
ribonucleic acid (mRNA) levels for these proteins from 1) women who were in
various stages of the menstrual cycle and 2) multiple leiomyomas from the
same patient. Immunohistochemical staining showed that fibronectin was
localized primarily around individual smooth muscle cells (SMC). Collagen
type I was distributed across the ECM and also in the cytoplasm of SMC.
Collagen type III was found primarily in the ECM. Leiomyomas showed more
intense staining for collagen types I and III than corresponding normal
myometrium. Northern blot and densitometric analysis showed that both
collagen type I and III mRNAs were consistently elevated in leiomyomas
relative to the adjacent myometrium in patients who were in the
proliferative phase of the menstrual cycle (P < 0.02 for both). These
differences were not evident in the secretory phase. Fibronectin mRNA
levels were quite variable, and there were no significant differences
between the two tissues at any stage of the menstrual cycle. We conclude
that leiomyomas show increased levels of mRNA for collagen types I and III
relative to the normal myometrium. However, this difference is only
manifested during the proliferative phase of the menstrual cycle. These
findings suggest that leiomyomas may be more sensitive to the hormonal
changes that occur during the menstrual cycle than is normal myometrium.
This article has been cited by other articles:
F. S. Mesquita, S. N. Dyer, D. A. Heinrich, S. E. Bulun, E. E. Marsh, and R. A. Nowak Reactive Oxygen Species Mediate Mitogenic Growth Factor Signaling Pathways in Human Leiomyoma Smooth Muscle Cells
Biol Reprod,
February 1, 2010;
82(2):
341 - 351.
[Abstract][Full Text][PDF]
J. M. Norian, M. Malik, C. Y. Parker, D. Joseph, P. C. Leppert, J. H. Segars, and W. H. Catherino Transforming Growth Factor {beta}3 Regulates the Versican Variants in the Extracellular Matrix-Rich Uterine Leiomyomas
Reproductive Sciences,
December 1, 2009;
16(12):
1153 - 1164.
[Abstract][PDF]
S. Nurmenniemi, T. Sinikumpu, I. Alahuhta, S. Salo, M. Sutinen, M. Santala, J. Risteli, P. Nyberg, and T. Salo A Novel Organotypic Model Mimics the Tumor Microenvironment
Am. J. Pathol.,
September 1, 2009;
175(3):
1281 - 1291.
[Abstract][Full Text][PDF]
A. Morikawa, N. Ohara, Q. Xu, K. Nakabayashi, D. A. DeManno, K. Chwalisz, S. Yoshida, and T. Maruo Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer
Hum. Reprod.,
April 1, 2008;
23(4):
944 - 951.
[Abstract][Full Text][PDF]
M.H. Hassan, N. Khatoon, D.T. Curiel, F.M. Hamada, H.M. Arafa, and A. Al-Hendy Toward gene therapy of uterine fibroids: targeting modified adenovirus to human leiomyoma cells
Hum. Reprod.,
March 1, 2008;
23(3):
514 - 524.
[Abstract][Full Text][PDF]
Q. Xu, N. Ohara, J. Liu, M. Amano, R. Sitruk-Ware, S. Yoshida, and T. Maruo Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells
Mol. Hum. Reprod.,
March 1, 2008;
14(3):
181 - 191.
[Abstract][Full Text][PDF]
S. A. Salama, A. B. Nasr, R. K. Dubey, and A. Al-Hendy Estrogen Metabolite 2-Methoxyestradiol Induces Apoptosis and Inhibits Cell Proliferation and Collagen Production in Rat and Human Leiomyoma Cells: A Potential Medicinal Treatment for Uterine Fibroids
Reproductive Sciences,
December 1, 2006;
13(8):
542 - 550.
[Abstract][PDF]
N. Takemura, S. Yoshida, S. Kennedy, M. Deguchi, N. Ohara, and T. Maruo Matrix Metalloproteinase-1 and -9 Promoter Polymorphisms Are Not Associated With an Increased Risk of Uterine Leiomyomas in a Japanese Population
Reproductive Sciences,
April 1, 2006;
13(3):
232 - 236.
[Abstract][PDF]
E. Levens, X. Luo, L. Ding, R. S. Williams, and N. Chegini Fibromodulin is expressed in leiomyoma and myometrium and regulated by gonadotropin-releasing hormone analogue therapy and TGF-{beta} through Smad and MAPK-mediated signalling
Mol. Hum. Reprod.,
July 1, 2005;
11(7):
489 - 494.
[Abstract][Full Text][PDF]
A. A. Arslan, L. I. Gold, K. Mittal, T.-C. Suen, I. Belitskaya-Levy, M.-S. Tang, and P. Toniolo Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review
Hum. Reprod.,
April 1, 2005;
20(4):
852 - 863.
[Abstract][Full Text][PDF]
X. Luo, L. Ding, J. Xu, R. S. Williams, and N. Chegini Leiomyoma and Myometrial Gene Expression Profiles and Their Responses to Gonadotropin-Releasing Hormone Analog Therapy
Endocrinology,
March 1, 2005;
146(3):
1074 - 1096.
[Abstract][Full Text][PDF]
T. Maruo, N. Ohara, J. Wang, and H. Matsuo Sex steroidal regulation of uterine leiomyoma growth and apoptosis
Hum. Reprod. Update,
May 1, 2004;
10(3):
207 - 220.
[Abstract][Full Text][PDF]
H. Shime, M. Kariya, A. Orii, C. Momma, T. Kanamori, K. Fukuhara, T. Kusakari, Y. Tsuruta, K. Takakura, T. Nikaido, et al. Tranilast Inhibits the Proliferation of Uterine Leiomyoma Cells in Vitro through G1 Arrest Associated with the Induction of p21waf1 and p53
J. Clin. Endocrinol. Metab.,
December 1, 2002;
87(12):
5610 - 5617.
[Abstract][Full Text][PDF]
X. Wu, A. Blanck, G. Norstedt, L. Sahlin, and A. Flores-Morales Identification of genes with higher expression in human uterine leiomyomas than in the corresponding myometrium
Mol. Hum. Reprod.,
March 1, 2002;
8(3):
246 - 254.
[Abstract][Full Text][PDF]
E. A. Stewart Gonadotropins and the Uterus: Is There a Gonad-Independent Pathway?
Reproductive Sciences,
December 1, 2001;
8(6):
319 - 326.
[Abstract][PDF]
D. Sampath, Y. Zhu, R. C. Winneker, and Z. Zhang Aberrant Expression of Cyr61, a Member of the CCN (CTGF/Cyr61/Cef10/NOVH) Family, and Dysregulation by 17{beta}-Estradiol and Basic Fibroblast Growth Factor in Human Uterine Leiomyomas
J. Clin. Endocrinol. Metab.,
April 1, 2001;
86(4):
1707 - 1715.
[Abstract][Full Text]
N. Chegini, X.-M. Tang, and C. Ma Regulation of Transforming Growth Factor-{beta}1 Expression by Granulocyte Macrophage-Colony-Stimulating Factor in Leiomyoma and Myometrial Smooth Muscle Cells
J. Clin. Endocrinol. Metab.,
November 1, 1999;
84(11):
4138 - 4143.
[Abstract][Full Text]
S. S. Palmer, D. Haynes-Johnson, T. Diehl, and R. A. Nowak Increased Expression of Stromelysin 3 mRNA in Leiomyomas (Uterine Fibroids) Compared With Myometrium
Reproductive Sciences,
July 1, 1998;
5(4):
203 - 209.
[Abstract][PDF]
B.-S. Lee, S. B. Margolin, and R. A. Nowak Pirfenidone: A Novel Pharmacological Agent That Inhibits Leiomyoma Cell Proliferation and Collagen Production
J. Clin. Endocrinol. Metab.,
January 1, 1998;
83(1):
219 - 223.
[Abstract][Full Text]
J. Andersen and R. L. Barbieri Abnormal Gene Expression in Uterine Leiomyomas
Reproductive Sciences,
September 1, 1995;
2(5):
663 - 672.
[Abstract][PDF]
J. Andersen, V. M. DyReyes, R. L. Barbieri, D. M. Coachman, and R. J. Miksicek Leiomyoma Primary Cultures Have Elevated Transcriptional Response to Estrogen Compared With Autologous Myometrial Cultures
Reproductive Sciences,
May 1, 1995;
2(3):
542 - 551.
[Abstract][PDF]
E. Levens, X. Luo, L. Ding, R. S. Williams, and N. Chegini Fibromodulin is expressed in leiomyoma and myometrium and regulated by gonadotropin-releasing hormone analogue therapy and TGF-{beta} through Smad and MAPK-mediated signalling
Mol. Hum. Reprod.,
July 1, 2005;
11(7):
489 - 494.
[Abstract][Full Text][PDF]
