OBJECTIVE: Human ovarian carcinoma samples were orthotopically implanted into SCID mice to investigate the contribution of matrix metalloproteases (MMPs) to the spread of ovarian tumors. METHODS: Mice were inoculated with patient tumor samples, and developed ovarian tumors over a 16-week period with metastasis occurring in some mice. Species-specific quantitative RT-PCR was used to identify the source of tumor-associated MMPs. RESULTS: Membrane-type (MT)1-MMP mRNA was significantly increased in high-grade tumors, tumors with evidence of serosal involvement, and tumors in which distant metastases were detected. The increase in MT1-MMP expression was predominantly from the human tumor cells, with a minor contribution from the mouse ovarian stroma. Neither human nor mouse MT2-MMP were correlated with tumor progression and MT3-MMP levels were negligible. While tumor cells did not produce significant amounts of MMP-2 or MMP-9, the presence of tumor was associated with increased levels of MMP-2 expression by mouse ovarian stroma. Stromal-derived MT1-MMP was greater in large tumors and was associated with stromal MMP-2 expression but neither was significantly linked with metastasis. CONCLUSIONS: These studies indicate that tumor-derived MT1-MMP, more so than other gelatinolytic MMPs, is strongly linked to aggressive tumor behavior. This orthotopic model of human ovarian carcinoma is appropriate for studying ovarian tumor progression, and will be valuable in the further investigation of the metastatic process.
OBJECTIVE:Humanovarian carcinoma samples were orthotopically implanted into SCIDmice to investigate the contribution of matrix metalloproteases (MMPs) to the spread of ovarian tumors. METHODS:Mice were inoculated with patienttumor samples, and developed ovarian tumors over a 16-week period with metastasis occurring in some mice. Species-specific quantitative RT-PCR was used to identify the source of tumor-associated MMPs. RESULTS:Membrane-type (MT)1-MMP mRNA was significantly increased in high-grade tumors, tumors with evidence of serosal involvement, and tumors in which distant metastases were detected. The increase in MT1-MMP expression was predominantly from the humantumor cells, with a minor contribution from the mouseovarian stroma. Neither human nor mouseMT2-MMP were correlated with tumor progression and MT3-MMP levels were negligible. While tumor cells did not produce significant amounts of MMP-2 or MMP-9, the presence of tumor was associated with increased levels of MMP-2 expression by mouseovarian stroma. Stromal-derived MT1-MMP was greater in large tumors and was associated with stromal MMP-2 expression but neither was significantly linked with metastasis. CONCLUSIONS: These studies indicate that tumor-derived MT1-MMP, more so than other gelatinolytic MMPs, is strongly linked to aggressive tumor behavior. This orthotopic model of humanovarian carcinoma is appropriate for studying ovarian tumor progression, and will be valuable in the further investigation of the metastatic process.
Authors: E Lengyel; J E Burdette; H A Kenny; D Matei; J Pilrose; P Haluska; K P Nephew; D B Hales; M S Stack Journal: Oncogene Date: 2013-08-12 Impact factor: 9.867
Authors: Christine L Chaffer; Bonnie Dopheide; Daniel R McCulloch; Allan B Lee; Jane M Moseley; Erik W Thompson; Elizabeth D Williams Journal: Clin Exp Metastasis Date: 2005 Impact factor: 5.150
Authors: Jennifer M Atkinson; Robert A Falconer; Dylan R Edwards; Caroline J Pennington; Catherine S Siller; Steven D Shnyder; Michael C Bibby; Laurence H Patterson; Paul M Loadman; Jason H Gill Journal: Cancer Res Date: 2010-07-27 Impact factor: 12.701
Authors: Aparna A Kamat; Mavis Fletcher; Lynn M Gruman; Peter Mueller; Adriana Lopez; Charles N Landen; Liz Han; David M Gershenson; Anil K Sood Journal: Clin Cancer Res Date: 2006-03-15 Impact factor: 12.531