Endometase/Matrilysin-2 in Human Breast Ductal Carcinoma <b>
                     <i>in Situ</i>
                  </b> and Its Inhibition by Tissue Inhibitors of Metalloproteinases-2 and -4

Zhao, Yunge; Xiao, Aizhen; Park, Hyun I.; Newcomer, Robert G.; Yan, Mei; Man, Yan‐gao; Heffelfinger, Sue C.; Sang, Qing‐Xiang Amy

doi:10.1158/0008-5472.can-03-1932

Cited by 86 publications

(104 citation statements)

References 43 publications

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“…As HGPIN is considered the preinvasive precursor form of prostate cancer, the study by Lee et al implicates that the expression of MMP-26 and TIMP-4 is coordinately regulated during disease progression. This finding is reminiscent of the authors' earlier study in breast cancer, where they showed that the expression of MMP-26 and TIMP-4 is significantly higher in preinvasive ductal carcinoma in situ comparing to invasive ductal carcinoma, hyperplasia, and normal breast epithelia [3]. While the functional significance of the apparently coordinated expression pattern of MMP-26 and TIMP-4 during malignant transition remains to be deciphered, these results suggest that peak expression of MMP-26 and TIMP-4 may underlie the conversion from noninvasive to invasive growth by the tumors.…”

supporting

confidence: 78%

Peaking of MMP-26 and TIMP-4 marks invasive transition in prostate cancer

2006

Cell Res

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Prostate cancer is one of the leading health threats to man, and like many other cancers, early detection and treatment is crucial to improving the prognosis of patients. Progression of the disease from noninvasive high-grade prostatic intraepithelial neoplasia (HGPIN) to invasive adenocarcinoma is linked to the action of a group of proteolytic enzymes called matrix metalloproteinases (MMPs), which digest various components of the extracellular matrix and thus open ways for tumor metastasis. Previous studies have shown that one MMP, MMP-26, is expressed at a significantly higher level in human prostate carcinoma than in normal prostate tissues, and that it appears to play an important role in promoting invasion of prostate cancer cells [1]. In this issue of Cell Research, Lee et al. report detailed analyses of the expression pattern of MMP-26, along with its most potent endogenous inhibitor, TIMP-4 (TIMP stands for tissue inhibitor of metalloproteinases), in a number of prostate cancer samples derived from human patients [2]. Interestingly, they found that both MMP-26 and TIMP-4 exhibit the highest expression in HGPIN; and the levels of both proteins are significantly lower in adjacent cancer areas in the same tissues [2]. Consistent with earlier results, the lowest expression of MMP-26 (and TIMP-4) was found in non-neoplastic tissues. As HGPIN is considered the preinvasive precursor form of prostate cancer, the study by Lee et al. implicates that the expression of MMP-26 and TIMP-4 is coordinately regulated during disease progression. This finding is reminiscent of the authors' earlier study in breast cancer, where they showed that the expression of MMP-26 and TIMP-4 is significantly higher in preinvasive ductal carcinoma in situ comparing to invasive ductal carcinoma, hyperplasia, and normal breast epithelia [3]. While the functional significance of the apparently coordinated expression pattern of MMP-26 and TIMP-4 during malignant transition remains to be deciphered, these results suggest that peak expression of MMP-26 and TIMP-4 may underlie the conversion from noninvasive to invasive growth by the tumors. Moreover, the highest expression of these factors in HGPIN raises the possibility that they could be used as new biomarkers for early diagnosis of a subset of prostate cancer patients before metastasis.

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supporting

confidence: 78%

Peaking of MMP-26 and TIMP-4 marks invasive transition in prostate cancer

2006

Cell Res

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“…Under normal conditions, MMPs and TIMPs are expressed at low levels in most adult tissues, but may become upregulated in pathophysiologic conditions such as wound healing and tumor progression. Mimicking the expression pattern of MMP-26, TIMP-4 expression in human breast DCIS is significantly higher than that detected in IDC, AIDH, and in normal breast epithelium adjacent to DCIS and IDC [13]. The therapeutic potential of TIMP-4 in the treatment of malignant progression has been examined, and the transfection of TIMP-4 cDNA into human MDA-MB-435 breast cancer cells inhibited tumor cell invasion across Matrigel, a barrier of reconstituted basement membrane components [20].…”

Section: Introductionmentioning

confidence: 82%

“…Our previous studies have shown that MMP-26 expression in human prostate carcinoma is significantly higher than that in prostatitis, benign prostate hyperplasia (BPH), and normal prostate tissue [12]. In addition, our group has shown that the expression of MMP 26 in human breast tissue is significantly higher during preinvasive ductal carcinoma in situ (DCIS) when compared to infiltrating ductal carcinoma (IDC), atypical intraductal hyperplasia (AIDH), and normal breast epithelia adjacent to DCIS and IDC [13]. These results suggest that MMP-26 plays an important role in the early stage prior to the development of invasive breast and prostate cancers.…”

Section: Introductionmentioning

confidence: 89%

“…Four members of the human TIMP family have been identified as follows: TIMP-1, TIMP-2, TIMP-3, and TIMP-4 [14][15][16][17]. The cleavage of synthetic peptides in vitro by MMP-26 is inhibited by TIMP-1, TIMP-2, and TIMP-4, with TIMP-4 displaying the greatest inhibitory potency [7,13]. TIMP-4 is a tight-binding and slow-binding inhibitor of MMP-26, with an apparent K i value of 0.62 nM [13].…”

Section: Introductionmentioning

confidence: 99%

“…The cleavage of synthetic peptides in vitro by MMP-26 is inhibited by TIMP-1, TIMP-2, and TIMP-4, with TIMP-4 displaying the greatest inhibitory potency [7,13]. TIMP-4 is a tight-binding and slow-binding inhibitor of MMP-26, with an apparent K i value of 0.62 nM [13]. TIMP-4 mRNA has been detected in a variety of normal tissues, including those of the heart, kidney, pancreas, colon, testis, endometrium, and placenta [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

et al. 2006

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The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 (MMP-26) promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 (TIMP-4) is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher (p<0.0001) MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer (p<0.001 for each) in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.

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GM‐CSF enhances tumor invasion by elevated MMP‐2, ‐9, and ‐26 expression

et al. 2012

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Granulocyte–macrophage colony-stimulating factor (GM-CSF) promotes tumor progression in different tumor models in an autocrine and paracrine manner. However, at the same time GM-CSF is used in cancer therapies to ameliorate neutropenia. We have previously shown in GM-CSF and G-CSF expressing or negative skin or head and neck squamous cell carcinoma that GM-CSF expression is associated with a highly angiogenic and invasive tumor phenotype. To determine the functional contribution of GM-CSF to tumor invasion, we stably transfected a GM-CSF negative colon adenocarcinoma cell line HT-29 with GM-CSF or treated the same cell line with exogenous GM-CSF. While GM-CSF overexpression and treatment reduced tumor cell proliferation and tumor growth in vitro and in vivo, respectively, it contributed to tumor progression. Together with an enhanced migratory capacity in vitro, we observed a striking increase in tumor cell invasion into the surrounding tissue concomitant with the induction of an activated tumor stroma in GM-CSF overexpressing or GM-CSF treated tumors. In a complex 3D in vitro model, enhanced GM-CSF expression was associated with a discontinued basement membrane deposition that might be mediated by the increased expression and activation of MMP-2, -9, and -26. Treatment with GM-CSF blocking antibodies reversed this effect. The increased presence and activity of these tumor cell derived proteases was confirmed in vivo. Here, expression of MMP-26 protein was predominantly located in pre- and early-invasive areas suggesting MMP-26 expression as an early event in promoting GM-CSF dependent tumor invasion.

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Endometase/Matrilysin-2 in Human Breast Ductal Carcinoma in Situ and Its Inhibition by Tissue Inhibitors of Metalloproteinases-2 and -4

Cited by 86 publications

References 43 publications

Peaking of MMP-26 and TIMP-4 marks invasive transition in prostate cancer

Peaking of MMP-26 and TIMP-4 marks invasive transition in prostate cancer

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

GM‐CSF enhances tumor invasion by elevated MMP‐2, ‐9, and ‐26 expression

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