MMP11: A Novel Target Antigen for Cancer Immunotherapy

Peruzzi, Daniela; Mori, Federica; Conforti, Antonella; Lazzaro, Domenico; Rinaldis, Emanuele de; Ciliberto, Gennaro; Monica, Nicola La; Aurisicchio, Luigi

doi:10.1158/1078-0432.ccr-08-3226

Cited by 82 publications

(61 citation statements)

References 35 publications

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“…Several genes that contribute to extracellular matrix remodeling, including Mmp10, Mmp3, Fbln, Krt7, and Muc1, can contribute to increased tumor invasion. Aberration to cell cycle regulators, such as the S100s, can cause unchecked growth, and changes to the regulation of cell signaling components Ret, Stat5a, Fzd10, Cxcl1, and Wif1 can lead to uncontrolled growth and differentiation (24,(34)(35)(36)(37). The abnormal response of these genes to E2 stimulation as a result of BPA treatment in utero is a particularly interesting link to the development of estrogen-sensitive cancers.…”

Section: Discussionmentioning

confidence: 99%

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol‐A) exposure

2016

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Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-a (ERa)-binding genes. The majority of genes that demonstrated both altered expression and ERa binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERa. Geneenvironment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogenrelated disease in adults.-Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure. FASEB J. 30, 3194-3201 (2016). www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol‐A) exposure

2016

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“…MMP II is expressed in 71% of esophageal cancer and may be an early event in esophageal tumorigenesis (18). Its expression in colorectal cancer (CRC) is associated with females, distal locations, infiltrative growth patterns and microsatellite stability of the patients (19,20), and even represents a novel expressed tumor associated antigen as the target candidate for CRC immunotherapy (21).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of MMP11 Inhibits Proliferation and Invasion of Gastric Cancer Cells

et al. 2013

Int J Immunopathol Pharmacol

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Matrix metalloproteinase 11(MMPll or stromelysin-3) has recently been reported to playa crucial role in the development and progression of multiple malignancies. The aim of this study was to investigate the function ofMMPll expression in human gastric adenocarcinoma (GAC). Using immunohistochemistry assay, we studied the expression level of MMPll in GAC and adjacent non-cancerous tissues (ANCT). The association between MMPll expression and tumor size and pathological grade, as well as metastatic potential was analyzed. Through small hairpin RNA (shRNA)-mediated MMPll knockdown in SGC-7901 GAC cells, we observed the changes of the biological behaviors of GAC cells. Our results indicated that the rate of positive expression ofMMPll was higher in GAC tissues than in ANCT (55.0% vs 30.0%, P=0.025). MMPll expression had no association with the factors of age or gender of the GAC patients, or the size, pathological staging and lymph node metastases of the tumors (each P>0.05). Furthermore, MMPll knockdown inhibited the proliferative activities and invasive potential of SGC-7901 GAC cells with decreased expression of IGF-l, PCNA and VEGF. Taken together, our findings demonstrated that MMPll expression was increased in GAC tissues, but did not correlate with the clinicopathologic features. Knockdown of MMPll expression could inhibit the proliferation and invasion of GAC cells probably through down-regulation of the IGF-l signaling pathway, suggesting that MMPll might be a potential therapeutic target for the treatment of gastric cancer.Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. The prognosis of gastric cancer is poor with an estimated relative five year survival rate of less than 20% (1). Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. Molecular oncobiology studies have brought to light a number of genes that are implicated in gastric carcinogenesis (2).Matrix metalloproteases (MMPs) playa key role in the metabolism of connective tissue proteins in the norm and in pathology. Major MMP subfamilies and matrixins act through promoting the oncogenic transformation of the cells, and angiogenesis (3). MMPs constitute one of the major extracellular matrix degrading enzymic families implicated in cancer development. MMP11 in particular, a member of the matrix metalloproteinases, exhibits collagenolytic function against collagen VI under normal and malignant conditions (4), and is closely related to invasiveness and tumor progression (5). MMP-ll expression is simulated in mouse

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“…3B). Further RT-PCR analyses revealed that the expression of matrix metalloproteinases MMP10, MMP11, and MMP14, which reportedly facilitate cancer cell invasion (17)(18)(19), was enhanced in PHD3kd tumor cells (Fig. 3C).…”

Section: Inhibition Of Phd3 Enhances Tumorigenicity In Vitromentioning

confidence: 96%

Prolyl Hydroxylase 3 Attenuates MCL-1–Mediated ATP Production to Suppress the Metastatic Potential of Colorectal Cancer Cells

et al. 2016

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Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance of PHD enzymes during the metastatic spread of colorectal cancer. PHD expression analysis in 124 colorectal cancer patients revealed that reduced tumoral expression of PHD3 correlated with increased frequency of distant metastases and poor outcome. Tumorigenicity and metastatic potential of colorectal tumor cells over and underexpressing PHD3 were investigated in orthotopic and heterotopic tumor models. PHD3 overexpression in a syngeneic tumor model resulted in fewer liver metastases, whereas PHD3 knockdown induced tumor spread. The migration of PHD3-overexpressing tumor cells was also attenuated in vitro. Conversely, migratory potential and colony formation were enhanced in PHD3-deficient cells, and this phenotype was associated with enhanced mitochondrial ATP production. Furthermore, the effects of PHD3 deficiency were accompanied by increased mitochondrial expression of the BCL-2 family member, member myeloid cell leukemia sequence 1 (MCL-1), and could be reversed by simultaneous inhibition of MCL-1. MCL-1 protein expression was likewise enhanced in human colorectal tumors expressing low levels of PHD3. Therefore, we demonstrate that downregulation of PHD3 augments metastatic spread in human colorectal cancer and identify MCL-1 as a novel downstream effector of oxygen sensing. Importantly, these findings offer new insight into the possible, context-specific deleterious effects of pharmacologic PHD inhibition. Cancer Res; 76(8); 2219-30. Ó2016 AACR.

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MMP11: A Novel Target Antigen for Cancer Immunotherapy

Cited by 82 publications

References 35 publications

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol‐A) exposure

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol‐A) exposure

Knockdown of MMP11 Inhibits Proliferation and Invasion of Gastric Cancer Cells

Prolyl Hydroxylase 3 Attenuates MCL-1–Mediated ATP Production to Suppress the Metastatic Potential of Colorectal Cancer Cells

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