Prominent expression of metalloproteinases in early stages of ovarian tumorigenesis

Kathy Qi Cai, Wan Lin Yang, Callinice D. Capo-Chichi, Lisa Vanderveer, Hong Wu, Andrew K. Godwin, Xiangxi Xu

Research output: Contribution to journalArticle

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Abstract

The role for matrix metalloproteinases (MMPs) in tumor cells invasion and metastasis is well established, and expression of MMPs is recognized as an indication of tumor cell malignancy. Previous studies suggest that the degradation of the basement membrane is a crucial early step in epithelial transformation and ovarian tumorigenesis. Thus, MMPs may also express and exert a role in preneoplastic lesions of ovarian tissues. We investigated the expression of the major metalloproteinases, gelatinase A, 72 kDa type IV collagenase (MMP-2), and gelatinase B, 92 kDa type IV collagenase (MMP-9), and the presence of basement membrane in ovarian tumors and tissues from prophylactic oophorectomies using immunostaining. MMP expression was also characterized in a panel of ovarian cancer cell lines and several nontumorigenic ovarian surface epithelial primary cells by zymography, Northern, and Western blots. We found, surprisingly, that MMP-2 and MMP-9 are expressed more frequently in early lesions than in established carcinomas. No correlation was found between the expression of MMPs and tumor grades or stages. In preneoplastic lesions, MMP-2 or MMP-9 expression often associates with the absence of basement membrane and morphological alterations. MMP-2 is often expressed in nontumorigenic ovarian surface epithelial cells but reduced or absent in cancer cells. Thus, we conclude that MMPs expression does not correlate with the malignancy of ovarian epithelial cells as generally thought. Rather, increased metalloproteinase expression is an early event in ovarian tumorigenesis and associates with the loss of epithelial basement membrane and morphological transformation. We propose that the increased MMP activity is an etiological factor for ovarian cancer risk. We found that MMPs expression does not correlate with the malignancy of ovarian epithelial cells as generally thought. Rather, increased metalloproteinase expression is an early event in ovarian tumorigenesis. The finding suggests roles of MMP in tumor initiation in addition to invasion, and may impact on the strategy for use of MMP inhibitors in cancer prevention.

Original languageEnglish
Pages (from-to)130-143
Number of pages14
JournalMolecular Carcinogenesis
Volume46
Issue number2
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

Fingerprint

Metalloproteases
Matrix Metalloproteinases
Carcinogenesis
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Neoplasms
Basement Membrane
Epithelial Cells
Ovarian Neoplasms
Matrix Metalloproteinase Inhibitors
Ovariectomy
Northern Blotting
Western Blotting
Neoplasm Metastasis
Carcinoma
Cell Line

Keywords

  • Basement membrane
  • Epithelium
  • MMPs
  • Ovarian cancer
  • Preneoplastic changes

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Cai, K. Q., Yang, W. L., Capo-Chichi, C. D., Vanderveer, L., Wu, H., Godwin, A. K., & Xu, X. (2007). Prominent expression of metalloproteinases in early stages of ovarian tumorigenesis. Molecular Carcinogenesis, 46(2), 130-143. https://doi.org/10.1002/mc.20273

Prominent expression of metalloproteinases in early stages of ovarian tumorigenesis. / Cai, Kathy Qi; Yang, Wan Lin; Capo-Chichi, Callinice D.; Vanderveer, Lisa; Wu, Hong; Godwin, Andrew K.; Xu, Xiangxi.

In: Molecular Carcinogenesis, Vol. 46, No. 2, 01.02.2007, p. 130-143.

Research output: Contribution to journalArticle

Cai, KQ, Yang, WL, Capo-Chichi, CD, Vanderveer, L, Wu, H, Godwin, AK & Xu, X 2007, 'Prominent expression of metalloproteinases in early stages of ovarian tumorigenesis', Molecular Carcinogenesis, vol. 46, no. 2, pp. 130-143. https://doi.org/10.1002/mc.20273
Cai KQ, Yang WL, Capo-Chichi CD, Vanderveer L, Wu H, Godwin AK et al. Prominent expression of metalloproteinases in early stages of ovarian tumorigenesis. Molecular Carcinogenesis. 2007 Feb 1;46(2):130-143. https://doi.org/10.1002/mc.20273
Cai, Kathy Qi ; Yang, Wan Lin ; Capo-Chichi, Callinice D. ; Vanderveer, Lisa ; Wu, Hong ; Godwin, Andrew K. ; Xu, Xiangxi. / Prominent expression of metalloproteinases in early stages of ovarian tumorigenesis. In: Molecular Carcinogenesis. 2007 ; Vol. 46, No. 2. pp. 130-143.
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