Aberrant Expression of Disintegrin-Metalloprotease Proteins in the Formation and Progression of Uterine Cervical Cancer

Shaker, Mohammed; Yokoyama, Yuhki; Mori, Satoshi; Tsujimoto, Masahiko; Kawaguchi, Naomasa; Kiyono, Tohru; Nakano, Toru; Matsuura, Nariaki

doi:10.1159/000324314

Cited by 6 publications

(6 citation statements)

References 97 publications

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“…Though particularly in squamous cell carcinoma, ADAM9 protein overexpression is also present in cancer of the cervix, the esophagus, the pharynx, the larynx, and the skin around the head and neck region (9,21,25,26). However, few previous studies have demonstrated no significant difference in ADAM9 mRNA expression between OSCC and normal tissues, or between oral cancer cell lines and normal oral keratinocytes (9,28), a finding that differs from our results on ADAM9 protein overexpression.…”

Section: Discussioncontrasting

confidence: 99%

“…In this study, a significant increase in ADAM9 protein expression in OSCC tissues, compared with in normal oral tissues, was demonstrated by immunohistochemistry, a finding that agrees with the results of other prior studies, which demonstrated ADAM9 protein overexpression in various types of cancer (9,15,17,18,(20)(21)(22)(23)25,26). Though particularly in squamous cell carcinoma, ADAM9 protein overexpression is also present in cancer of the cervix, the esophagus, the pharynx, the larynx, and the skin around the head and neck region (9,21,25,26).…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, ADAM9 can function in both physiological and pathological conditions. Regarding its involvement in pathologic conditions, ADAM9 overexpression has been identified in a variety of cancer types, including breast cancer (16), renal cancer (17), prostate cancer (18), skin melanoma (19), uterine cervical cancer (20,21), hepatocellular carcinoma (22), non-small cell lung cancer (23), colon cancer (24), gastric cancer (15), esophageal cancer (25) and head and neck squamous cell carcinoma (HNSCC) (26). In the oral cavity, conflicting results of chromosomal aberrations in the ADAM9-containing region have been identified by the array comparative genomic hybridization technique (9,27).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of ADAM9 in oral squamous cell carcinoma

et al. 2017

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Abstract. Overexpression of a disintegrin and metalloproteinase 9 (ADAM9) has been shown in various types of cancer. Some studies have reported inconclusive findings regarding chromosomal aberrations in the ADAM9-containing region and ADAM9 expression in oral cancer. Therefore, in this study, ADAM9 protein expression was determined and compared between oral squamous cell carcinoma (OSCC) and normal oral tissues, and between oral cancer cell lines and human oral keratinocytes (HOKs). In total, 34 OSCC and 10 healthy paraffin-embedded tissue sections were probed with an anti-ADAM9 antibody, and the immunohistochemical score was determined by multiplying the percentage of positively stained cells with the intensity score. Four different oral cancer and eight independent HOK cell lines were cultured, and the expression of membrane ADAM9 and active ADAM9 at 84 kDa in these cell lines was assayed by flow cytometry and western blot hybridization, respectively. The results showed that the median immunohistochemical score of ADAM9 expression in OSCC tissues was significantly greater than that in normal tissues (P<0.001). Furthermore, among OSCC cases, intense staining of ADAM9 expression was detected in well-differentiated and in moderately-differentiated OSCC; ADAM9 expression was also correlated with an increased degree of cell differentiation (r=0.557; P=0.001). Expression of membrane ADAM9 was present in 3/4 cancer cell lines. Expression of active ADAM9 varied among all the tested cell lines, but significantly higher ADAM9 expression was present in certain cancer cell lines than those in HOKs (P<0.05). In summary, ADAM9 expression is enhanced in OSCC and oral cancer cell lines, suggesting its role in the pathogenesis of oral cancer. Similar to the overexpression of ADAM9 in well-differentiated prostate cancer, high degrees of ADAM9 expression have also been observed in well-differentiated OSCC.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Overexpression of ADAM9 in oral squamous cell carcinoma

et al. 2017

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“…Total RNA was extracted from normal epithelial and breast cancer cell lines as previously described [ 22 ]. The mRNA levels of SUV420H1 and SUV420H2 were quantitated by real-time PCR using a LightCycler 480 System (Roche Diagnostics, Basel, Switzerland) and normalized to the mRNA level of GAPDH (encoding glyceraldehyde-3-phosphate dehydrogenase).…”

Section: Methodsmentioning

confidence: 99%

Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity

et al. 2014

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IntroductionLoss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions.MethodsLevels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro.ResultsH4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro.ConclusionsH4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner.

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“…A study with contrasting findings has indicated that TIMP3 is upregulated in cervical cancer cell lines (HPV-related QG-U cells and HPV-negative Yumoto cells) and cervical SCC tissues [ 135 ]. Shaker et al created a model to induce LSIL, HSIL, and invasive cervical cancer by introducing genetic material into human cervical keratinocytes (HCK).…”

Section: Timp3 In Gynaecological Cancersmentioning

confidence: 99%

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology

Lee,

Wu,

Cheng

et al. 2024

IJMS

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Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

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Aberrant Expression of Disintegrin-Metalloprotease Proteins in the Formation and Progression of Uterine Cervical Cancer

Cited by 6 publications

References 97 publications

Overexpression of ADAM9 in oral squamous cell carcinoma

Overexpression of ADAM9 in oral squamous cell carcinoma

Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology

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