Urinary MMP-2 and MMP-9 predict the presence of ovarian cancer in women with normal CA125 levels

Coticchia, Christine M.; Curatolo, Adam S.; Zurakowski, David; Yang, Jiang; Daniels, Kathryn E.; Matulonis, Ursula A.; Moses, Marsha A.

doi:10.1016/j.ygyno.2011.07.034

Cited by 51 publications

(41 citation statements)

References 20 publications

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“…From this, no association was found between CA125 and HCMV pp65/IE expression levels. To further confirm this, we examined CA125 expression level and MMP2 and MMP9 expression levels (known as potential markers of aggressive ovarian cancer with normal CA125 [32]) using in vitro model. HCMV infection did not affect CA125 ( P  = .2) or MMP2 ( P  = .054) on either mRNA or protein levels, but significantly increased the expression of MMP9 in both transcript and protein ( P  = .002) (Figure 5).…”

Section: Resultsmentioning

confidence: 94%

“…Furthermore, MMP9 expression was significantly increased in HCMV infected ovarian cancer cells as shown in our in vitro study. MMP9 and MMP2 have been linked to ovarian cancer in patients with low or absent CA125 levels [32], where high levels indicate more aggressive ovarian cancers. CA125 is involved in the epithelial to mesenchymal transition and may have a role in metastatic disease [32], [48], [49].…”

Section: Discussionmentioning

confidence: 99%

“…MMP9 and MMP2 have been linked to ovarian cancer in patients with low or absent CA125 levels [32], where high levels indicate more aggressive ovarian cancers. CA125 is involved in the epithelial to mesenchymal transition and may have a role in metastatic disease [32], [48], [49]. Thus, HCMV-induced expression of MMP9 may be linked to a more aggressive phenotype of ovarian cancer with higher metastatic potential and poor outcome.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer

Rådestad¹,

Estekizadeh²,

Cui³

et al. 2018

Translational Oncology

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Human cytomegalovirus (HCMV) has been detected in various types of tumors. We studied the prevalence of HCMV in ovarian cancer and its relation to clinical outcome. Paraffin-embedded tissues obtained prospectively from 45 patients with ovarian cancer and 30 patients with benign ovarian cystadenoma were analyzed for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Plasma was analyzed for HCMV serology. HCMV-IgG levels were higher in patients with ovarian cancer or benign cystadenoma than in age-matched controls (P = .002, P < .0001, respectively). HCMV IgM was detected in 12% of ovarian cancer patients and 3% of patients with benign tumors but was absent in controls. In patients with ovarian cancer, higher IgG levels were associated with better outcomes (P = .04). Extensive HCMV-IE protein expression was detected in 75% of ovarian cancers and 26% of benign tumors; pp65 was detected in 67% of ovarian cancers and 14% of benign tumors. A higher grade of HCMV infection was associated with higher stage of disease. Extensive HCMV-pp65 expression was associated with shorter median overall survival than focal expression (39 versus 42.5 months, P = .03). At study closure, 58% of ovarian cancer patients with focal pp65 expression were alive versus 27% of patients with extensive pp65 expression (P = .03). Thus, HCMV proteins are detected at different levels in ovarian tumors and benign cystadenomas. Ovarian cancer patients with focal HCMV-pp65 expression in their tumors and high IgG levels against HCMV lived longer, highlighting a need for in-depth studies of the oncomodulatory role of HCMV in ovarian cancer.

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Section: Resultsmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer

Rådestad¹,

Estekizadeh²,

Cui³

et al. 2018

Translational Oncology

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show abstract

“…Coticchia and colleagues showed that MMP2 and MMP9 levels in the urine may be clinically helpful to diagnose ovarian cancer and their results were independent of CA125 levels (Coticchia et al 2011). Platelet derived growth factor D (PDGF-D) has been also shown to promote ovarian cancer invasion and this increase in invasion is caused by PDGF-D increasing the expression of MMP2 and MMP9 (Wang et al 2011b).…”

Section: Mmps and Ovarian Cancermentioning

confidence: 99%

Ovarian cancer: involvement of the matrix metalloproteinases

Al-Alem

Curry

2015

Reproduction

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Ovarian cancer is the leading cause of death from gynecologic malignancies. Reasons for the high mortality rate associated with ovarian cancer include a late diagnosis at which time the cancer has metastasized throughout the peritoneal cavity. Cancer metastasis is facilitated by the remodeling of the extracellular tumor matrix by a family of proteolytic enzymes known as the matrix metalloproteinases (MMPs). There are 23 members in the MMP family, many of which have been reported to be associated with ovarian cancer. In the current paradigm, ovarian tumor cells and the surrounding stromal cells stimulate the synthesis and/or activation of various MMPs to aid in tumor growth, invasion, and eventual metastasis. This review sheds light on the different MMPs in the various types of ovarian cancer and their impact on the progression of this gynecologic malignancy.

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“…STAT3 is an important transcription factor regulating the expression of a wide variety of proteins including MMPs, which are frequently upregulated in malignant tumor cells (42,43). In ovarian cancers, MMP-2 and MMP-9 are two of the most commonly elevated MMPs and contribute to the development of tumor metastasis and poor prognosis (44–48).…”

Section: Discussionmentioning

confidence: 99%

Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion

et al. 2017

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Metastasis is the major cause of death in ovarian cancer patients. Given that the molecular mechanism underlying metastasis formation is critical for improving therapeutic development and clinical treatment, it must be fully understood. Recent studies have revealed that lipid kinase type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) participates in the metastasis of breast cancer and colon cancer by regulating cell migration and invasion. However, its role in the progression of ovarian cancer is unclear. Here we showed that PIPKIγ expression is upregulated in multiple epithelial ovarian cancer cell lines. Silencing of PIPKIγ impaired PI3K/AKT signaling and inhibited the aggressive behaviors of epithelial ovarian cancer cells, including proliferation, migration and invasion. Moreover, we found that PIPKIγ was required for the activation of signal transducer and activator of transcription 3 (STAT3) in epithelial ovarian cancer cells, indicating that STAT3 may also be engaged in the PIPKIγ-dependent aggressiveness of epithelial ovarian cancer cells. Our results, for the first time, identified PIPKIγ as a novel regulator in epithelial ovarian cancer cells that promotes cell proliferation, migration and invasion by activating multiple signaling pathways. Therefore, we propose that PIPKIγ could potentially be a therapeutic target for the early detection and treatment of epithelial ovarian cancer. Further studies employing in vivo models are necessary to test this possibility.

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Urinary MMP-2 and MMP-9 predict the presence of ovarian cancer in women with normal CA125 levels

Cited by 51 publications

References 20 publications

Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer

Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer

Ovarian cancer: involvement of the matrix metalloproteinases

Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion

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