Proteins with whey-acidic-protein motifs and cancer

Bouchard, D.; Morisset, Dany; Bourbonnais, Yves; Tremblay, Guy M.

doi:10.1016/s1470-2045(06)70579-4

Cited by 176 publications

(163 citation statements)

References 60 publications

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…40 PI3 and other genes of the WAP protein family are clustered on chromosome 20q12-13.1 and are frequently up-regulated in several solid tumors. 41 Interestingly, we could reproduce up-regulation of PI3/elafin in vitro, by both, serum deprivation and moderate hypoxia, suggesting a direct link between unfavorable growth conditions and PI3 expression.…”

Section: Discussionmentioning

confidence: 74%

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Saidi

Javerzat

Bellahcène

et al. 2007

Intl Journal of Cancer

101

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti‐angiogenic agents used increasingly in the clinic. However, to be efficient, anti‐VEGF agents need to be associated with classic chemotherapy. Exploring gene regulation in tumor cells during anti‐angiogenesis might help to comprehend the molecular basis of response to treatment. To generate a defined anti‐angiogenic condition in vivo, we transfected human glioma cells with short‐interfering RNAs against VEGF‐A and implanted them on the chick chorio‐allantoic membrane. Gene regulation in avascular tumors was studied using human Affymetrix™ GeneChips. Potentially important genes were further studied in glioma patients. Despite strong VEGF inhibition, we observed recurrent formation of small, avascular tumors. CHI3L2, IL1B, PI3/elafin and CHI3L1, which encodes for YKL‐40, a putative prognosticator for various diseases, including cancer, were strongly up‐regulated in avascular glioma. In glioblastoma patients, these genes showed coregulation and their expression differed significantly from low‐grade glioma. Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA (p = 0.0004) were significantly correlated with poor survival. Cox regression analysis further confirmed that PI3 and CHI3L1 levels are survival markers independent from patient age and sex. Elafin‐positive tumor cells were only found in glioblastoma, where they were clustered around necrotic areas. PI3/elafin is strongly induced by serum deprivation and hypoxia in U87 glioma cells in vitro. Our results indicate that anti‐angiogenesis in experimental glioma drives expression of critical genes which relate to disease aggressiveness in glioblastoma patients. In particular, CHI3L1 and PI3/elafin may be useful as new prognostic markers and new therapeutic targets. © 2007 Wiley‐Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 74%

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Saidi

Javerzat

Bellahcène

et al. 2007

Intl Journal of Cancer

101

View full text Add to dashboard Cite

show abstract

“…Several possible mechanisms for the promalignant activity of SLPI have been proposed (27). For instance, SLPI has been shown to stimulate fibroblasts to produce hepatocyte growth factor (28), a potent stimulator of tumor growth and progression (29).…”

Section: Discussionmentioning

confidence: 99%

The Tumor-Promoting Effect of TNF-α Involves the Induction of Secretory Leukocyte Protease Inhibitor

Devoogdt

Revets

Kindt

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

According to the cancer immunoediting concept, inflammatory mediators play not only a critical role in promoting host protection against cancer but also contribute to cancer cell growth and survival. TNF-α is a critical factor in this network. However, the mechanisms underlying the tumor-promoting effect of TNF-α have not been fully elucidated yet. We previously reported that in vitro culture of Lewis lung carcinoma 3LL cells with TNF-α-producing macrophages resulted in enhanced resistance toward TNF-α-mediated lysis and increased malignancy of the 3LL cells. In this study, we analyzed the effects of endogenous TNF-α on TNF-α resistance and malignant behavior in vivo of low-malignant/TNF-α-sensitive 3LL-S cells and cancer cells derived from 3LL-S tumors that developed in wild-type or TNF-α−/− mice. Interestingly, 3LL-S cells acquired a malignant phenotype in vivo depending on the presence of host TNF-α, whereas acquisition of TNF-α resistance was TNF-α-independent. This result suggested that malignancy-promoting characteristics of 3LL-S cells other than TNF-α resistance are influenced in vivo by TNF-α. We previously identified the malignancy-promoting genes, secretory leukocyte protease inhibitor (SLPI) and S100A4, as being up-regulated in 3LL-S cells upon their s.c. growth in wild-type mice. In this study, we show that SLPI, but not S100A4, was induced in 3LL-S cells both in vitro and in vivo by TNF-α, and that silencing of in vivo induced 3LL-S SLPI expression using RNA interference abrogated in vivo progression but did not influence TNF-α resistance. These data indicate that SLPI induction may be one mechanism whereby TNF-α acts as an endogenous tumor promoter.

show abstract

“…The HE4 is a glycoprotein, over expressed by EOC. High concentration have been detected in serum from OC patients, especially patients with serous and endometrioid adenocarcinoma (Bouchard et al, 2006;Drapkin et al, 2005;Van et al, 2011). Expression of HE4 in normal tissue is low, higher in non-ovarian cancer tissue and with the highest expression found in OC tissue (Galgano et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Many oncogenes achieve a high level of expression via genetic amplification. In humans, HE4, SLPI and several other WAP members co-locate in 20q (Bouchard et al, 2006) a region frequently amplified in a variety of cancers (Van Dekken et al, 2001). HE4, a putative protease inhibitor containing two WAP (Whey Acid Protein) domains (Li et al, 2013) has been used widely for the early screening (Winstead, 2009;Scholler et al, 2006) and for differential diagnosis (Huhtinen et al, 2009;Montagnana et al, 2009) of ovarian cancer, as well as for monitoring disease recurrence (Anastasi et al, 2010) and progression (Kobel et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Human Epididymis Protein 4 (HE4) mRNA as a Prognostic Marker in Ovarian Tumors in Relation to RMI and CA125

Yehia¹,

Mansour²,

Mekawy³

2015

International J. of Cancer Research

View full text Add to dashboard Cite

Human Epididymis protein 4 (HE4) has recently been shown to improve the sensitivity and specificity of Epithelial Ovarian Cancer (EOC) diagnosis but its function in cancer cells is not clear. We evaluated HE4 expression, RMI and CA125 serum level as diagnostic tools of primary ovarian cancer in Egyptian women. The HE4 gene expression was evaluated by real time PCR in ovarian cancer of 50 Egyptian women. Ovarian cancer tissues were studied for the detection of the gene expression of HE4 by Quantitative Real Time PCR (Q RT-PCR). Serum Human cancer antigen 125 (CA 125) was measured in the serum of all participants of the study using immune sorbent assay (ELISA). The HE4 showed significant difference among ovarian malignant tumors patients compared to the control subjects (p<0.01). The best cutoff value 0.053 at which HE4 sensitivity was 92% and specificity was 96%. There was a significance correlation between HE4, RMI and CA125 in all patients of the study (p#0.01 for both). The mRNA expression of HE4 was significantly high versus the control group in early stages and low grades of the disease (p = 0.00, 0.01, respectively). As well as, there was Increased HE4 expression in the late stages of the disease suggesting that it may be associated with poor prognosis as well. The HE4 could be considered as a good prognostic marker for ovarian cancer that increases the sensitivity of the CA 125 to absolute value without affection of CA125 accuracy and its positive predictive value.

show abstract

Proteins with whey-acidic-protein motifs and cancer

Cited by 176 publications

References 60 publications

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

The Tumor-Promoting Effect of TNF-α Involves the Induction of Secretory Leukocyte Protease Inhibitor

Human Epididymis Protein 4 (HE4) mRNA as a Prognostic Marker in Ovarian Tumors in Relation to RMI and CA125

Contact Info

Product

Resources

About