Secretory Leukocyte Protease Inhibitor in Cancer Development

Devoogdt, Nick

doi:10.1196/annals.1322.044

Cited by 50 publications

(46 citation statements)

References 32 publications

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“…SLPI is overexpressed in rarely developed inflammatory breast cancer with highly angiogenic and metastatic capacity (21). In addition, the overexpression of SLPI in lung carcinoma cells showed rapid tumorigenicity and lung metastasis upon subcutaneous inoculation compared to the control cells (7). The level of SLPI expression was higher in all types of ovarian cancers.…”

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

“…In addition, SLPI was reported to play a role not only in protecting the tissues from the protease (4) but also in promoting wound healing, cell proliferation, inhibiting HIV infections, anti-bacterial and anti-fungal activity (5,6). The overexpression of SLPI was reported to promote metastasis in lung carcinoma 3LL-S cells and oral carcinoma KB cells (7,8).Matrix metalloproteinases (MMPs) play important roles in normal physiological processes, such as embryogenesis, tissue remodeling and wound healing. The overexpression of MMPs is associated with many pathological abnormalities, such as atherosclerosis, tumor invasion and arthritic diseases (9).…”

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confidence: 99%

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Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells

Choi

Jeong²,

Wang³

et al. 2011

Int J Mol Med

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Abstract. Secretory leukocyte protease inhibitor (SLPI) protects tissue from proteases, and promotes cell proliferation and healing during inflammatory response. SLPI is also overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. Matrix metalloproteinases-2, -9 (MMP-2 and MMP-9) are overexpressed in high metastatic cancers, and promote the migration of cancer cells through collagen degradation. SLPI and MMP-2, -9 are critical factors in stimulating the metastatic processes but there are no reports of a direct correlation between these molecules. Therefore, this study examined the role of SLPI related to MMP-2 and MMP-9 using two gastric cancer cell lines, such as characterized non-metastatic SNU484 and highly metastatic SNU638 cells. SLPI, MMP-2 and MMP-9 mRNA and protein expression were higher in SNU638 cells than in SNU484 cells. In addition, the rate of cell migration and invasion was higher in the SNU638 cells than in SNU484 cells. Interestingly, after treatment with SLPI, the rate of migration and invasion was higher in the SNU484 cells than in the positive control (PC) SNU484 cells. The rate of migration was also higher in the SNU638 cells after SLPI treatment than in the SNU638 cells (PC) but the invasion rate was not changed. The expression and secretion of MMP-2 and MMP-9 as well the rate of cell migration and invasion were significantly lower in SLPIsiRNA transfected SNU638 cells (si-SLPI/SNU638) but higher in SLPI-treated SNU484 cells (SNU484 + SLPI). Strong Elk-1 phosphorylation was detected in SNU484 + SLPI and SNU638 cells but was barely detectable in SNU484 and si-SLPI/SNU638 cells. These results show that SLPI promotes the metastasis of SNU638 gastric cancer cells by increasing MMP-2 and MMP-9 expression through Elk-1 signaling, indicating its role as a signaling molecule not a protease inhibitor. IntroductionThe metastatic cascade of cancer cells is viewed as a series of sequential and interrelated steps, which include the following: epithelial-mesenchymal transition (EMT), degradation of the basement membrane; dissociation of tumor cells from the primary site; invasion of the neighboring tissue; intravasation into the blood and lymph vessels; transport through the vessels; extravasation from the vessels; and proliferation at a distant site. Among these processes, tumor cells invading the neighboring tissue after degrading the basement membrane is a major development (1).Secretory leukocyte protease inhibitor (SLPI) is an 11.7-kDa cystein-rich protein and an epithelial cell product found in saliva, seminal plasma and in the cervical, nasal, and bronchial mucus. SLPI inhibits the serine protease activity, such as chymotrypsin, trypsin, pancreatic elastase, cathepsin G, mast cell chymase (2). Recently, SLPI was reported to be an anti-inflammatory factor that contributes at the early inflammatory response in odontoblasts (3). In addition, SLPI was reported to play a role not only in protecting the tissues from the protease (4) but also in promoting wou...

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells

Choi

Jeong²,

Wang³

et al. 2011

Int J Mol Med

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“…5 Expression of SLPI and elafin has been identified in various carcinomas, and these genes may play a role in cancer development or progression. [25][26][27][28][29] In addition, amplification of 20q12-13 has been demonstrated specifically in breast and ovarian carcinomas. 30,31 Recent interest in HE4 has been generated by the consistent demonstration of overexpression in ovarian carcinomas in comparison to normal ovarian tissue.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of HE4 expression in normal and malignant human tissues

2006

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The HE4 (WFDC2) gene encodes a WAP-type four disulphide core domain-containing protein with a presumptive role in natural immunity. Multiple studies have consistently identified upregulation of HE4 gene expression in carcinomas of the ovary; however, the expression in normal and malignant adult tissues has not been examined in detail. Here, we examined the expression of the HE4 gene and protein in a large series of normal and malignant adult tissues by oligonucleotide microarray and tissue microarray, respectively. HE4 gene expression was highest in normal human trachea and salivary gland, and to a lesser extent, lung, prostate, pituitary gland, thyroid, and kidney. In a series of 175 human adult tumors, gene expression was highest in ovarian serous carcinomas. However, adenocarcinomas of the lung, and occasional breast, transitional cell and pancreatic carcinomas had moderate or high levels of HE4 expression. Using tissue microarrays and full tissue sections of normal and 448 neoplastic tissues, HE4 immunoreactivity was found in normal glandular epithelium of the female genital tract and breast, the epididymis and vas deferens, respiratory epithelium, distal renal tubules, colonic mucosa, and salivary glands, consistent with HE4 gene expression. In addition to consistent positivity in ovarian carcinoma, some pulmonary, endometrial, and breast adenocarcinomas, mesotheliomas, and less often, gastrointestinal, renal and transitional cell carcinomas were also positive. Knowledge of the expression patterns of HE4 in our survey is useful for application in histopathologic diagnosis, and should be taken into consideration in future studies that examine the role of HE4 as a serological tumor biomarker or as a target for gene-based therapy.

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“…35 Comparative genomic hybridization studies have shown the q12-13.1 locus on chromosome 20 is frequently amplified in gastric, oral, breast, ovarian, colon and pancreatic cancers. 36,37 These findings led to the proposal that genes located in this region may play undefined roles in carcinogenesis and tumour progression. Four WAP-domain proteins (secretory leucocyte protease inhibitor [SLPI], elafin, WFDC2 and WFDC1) have been identified as candidate molecular markers for cancer.…”

Section: Discussionmentioning

confidence: 99%

The Role of HE4 in Ovarian Cancer: Inhibiting Tumour Cell Proliferation and Metastasis

Cheng

et al. 2011

J Int Med Res

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As a promising biomarker, human epididymis protein 4 (HE4) has been widely used for the early detection and differential diagnosis of ovarian cancer. This study evaluated the function of HE4 in the carcinogenesis and progression of ovarian cancer. An enzyme immunometric assay, used to detect HE4 in the serum of ovarian cancer patients, showed that the protein could discriminate between malignant and benign ovarian tumours with high specificity. An exogenous HE4 gene was transfected into ovarian cancer cell lines and an immortalized ovarian epithelial cell line. Compared with the controls, HE4 overexpression significantly promoted cell apoptosis and adhesion. Overexpression of HE4 also led to significant inhibition of cell proliferation, migration and invasiveness in vitro, as well as xenograft tumour formation in vivo. This is the first report to demonstrate the functional importance of HE4 in multiple cellular processes and indicates that HE4 may play a protective role in the progression of ovarian cancer.

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Secretory Leukocyte Protease Inhibitor in Cancer Development

Cited by 50 publications

References 32 publications

Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells

Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells

Comprehensive analysis of HE4 expression in normal and malignant human tissues

The Role of HE4 in Ovarian Cancer: Inhibiting Tumour Cell Proliferation and Metastasis

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