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Matrix metalloproteinase 3 is a stromal marker for chicken ovarian cancer.

ABSTRACT: Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix and basement membranes. Due to this, MMPs have been thought to promote invasion and metastasis of cancer cells and angiogenesis in tumors. Even though the chicken is a useful animal model for studying human ovarian cancer, no reports exist of the MMP expression pattern in chicken ovarian cancer. Therefore, we investigated the expression pattern of MMPs in chicken ovarian cancer. Results of RT-PCR and quantitative RT-PCR analyses showed MMP3 to be over-expressed in cancerous hen ovaries. In situ hybridization analysis of cancerous chicken ovaries showed that MMP3 mRNA was predominantly localized in the stroma, which is similar to MMP3 expression in human cancers. The results suggest that the expression pattern of MMP3 mRNA in chicken ovarian cancer is similar to that in various types of human cancer. Moreover, MMP3 potentially plays a significant role in developing ovarian cancer in chickens. The cell type-specific expression of MMP3 makes this gene a unique marker for ovarian cancer in chickens.

SUBMITTER: Choi JW

PROVIDER: S-EPMC3406570 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Matrix metalloproteinase 3 is a stromal marker for chicken ovarian cancer.

Choi Jin Won JW Ahn Suzie E SE Rengaraj Deivendran D Seo Hee Won HW Lim Whasun W Song Gwonhwa G Han Jae Yong JY

Oncology letters 20110819 6

Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix and basement membranes. Due to this, MMPs have been thought to promote invasion and metastasis of cancer cells and angiogenesis in tumors. Even though the chicken is a useful animal model for studying human ovarian cancer, no reports exist of the MMP expression pattern in chicken ovarian cancer. Therefore, we investigated the expression pattern of MMPs in chicken ovarian cancer. Results of RT-PCR and qua ...[more]

PMID: 22848266

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Project description:Breast cancer survival rates decrease from 99% for patients with local disease to 25% for those with distant metastases. Matrix metalloproteinases (MMPs), including MMP2, are associated with metastatic progression. We found that loss of host MMP2 reduces the proliferation of experimental metastases in the lungs and identified fibroblasts in tumour-bearing lungs as the major source of MMP2. In vitro, spheroidal mammary tumour growth was increased by co-culture with control fibroblasts isolated from tumour-bearing lungs, but not when fibroblasts with stable Mmp2 knockdown were used. This result prompted us to assess whether MMP2 was responsible for a tumour-proliferative, activated fibroblast phenotype. To test this, we evaluated: (a) fibroblasts from wild-type tumour-bearing lungs, with or without shRNA-mediated MMP2 knockdown; and (b) normal, quiescent fibroblasts isolated from either WT or Mmp2(-/-) mice. Quantitative PCR revealed that Mmp2 knockdown attenuated expression of two markers of activation (?-smooth muscle actin and vimentin), but there was minimal expression in quiescent WT or Mmp2(-/-) fibroblasts, as expected. Placing quiescent fibroblasts under activating conditions led to increases in activation-associated transcripts in WT but not Mmp2(-/-) fibroblasts. Additionally, Mmp2 knockdown fibroblasts showed significantly decreased expression of the matrix transcripts collagen I, collagen IV and fibronectin. Addition of active TGF? was sufficient to rescue the MMP2-dependent collagen I and IV expression, while MMP2-induced collagen expression was blocked by the addition of TGF?1-neutralizing antibody. Gene expression data in stromal cells of human breast cancers reveal that MMP2 expression is also positively correlated with activation and matrix transcripts. Thus, we present a model whereby MMP2 production in tumour fibroblasts is important for TGF?1 activity and subsequent activation of fibroblasts to a matrix-producing, proliferation-supportive phenotype. Overall, our results reveal a previously undefined role for MMP2 in metastatic outgrowth mediated by fibroblasts, and extend the mechanisms by which MMPs contribute to tumour progression.

Dataset Information

Matrix metalloproteinase 3 is a stromal marker for chicken ovarian cancer.

Publications

Matrix metalloproteinase 3 is a stromal marker for chicken ovarian cancer.

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