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Entity | Breast cancer |
Note | MMP-26 is not expressed in normal mammary epithelium, is strongly upregulated in ductal carcinoma in situ (DCIS), and decreases throughout further disease progression (stages I to III). Co-expression of MMP-26 and TIMP-4 or MMP-9 has been detected in DCIS. Estrogen receptor-β (ER-β), not ER-α, is a substrate of MMP-26 in vivo and in vitro, indicating a novel regulation loop between estrogen and ER and modification of the ER-α/ER-β ratio. Additionally, silencing MMP-26 expression in the human breast cancer cell line MDA-MB-231 up-regulated the expression of five proteins (heat shock protein 90, glucose-regulated protein 78, annexin V, tropomyosin, peroxiredoxin II) and down-regulated the expression of four proteins (α-tubulin, cystatin SA-III, breast cancer metastasis suppressor 1 (BRMS1), and β-actin). |
Prognosis | MMP-26 expression is associated with ER+ human breast cancer and has positive correlation with patient survival in DCIS. |
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Entity | Endometrial cancer, ovarian cancer |
Note | MMP-26 mRNA is localized in the epithelial component of normal, hyperplastic, premalignant, and malignant samples of endometrial tissue and in situ hybridization indicates maximal levels in normal tissue (midcycle) and in endometrial hyperplasia (with and without atypia). Endometrial carcinomas exhibit greater expression compared to benign endometrium from the postmenopausal period, but not from the secretory phase of the menstrual cycle. Expression progressively decreases with loss of histological differentiation in malignant samples. Increased staining intensity correlates with grade III tumors and with the depth of myometrial invasion in tumors histologically characterized as endometrioid adenocarcinoma. Relating to ovarian cancer, MMP-26 is expressed in normal tissue as well as ovarian tumors with expression increasing with increased tumor stage. Invading ovarian tumor cells display the strongest expression of MMP-26, and progression of ovarian cancer is correlated with MMP-26 co-expression with TIMP-3, and TIMP-4. |
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Entity | Prostate cancer, prostatitis, benign prostate hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HGPIN) |
Note | Protein levels in human prostate carcinomas from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia (BPH), and normal prostate glandular tissue. MMP-26 and TIMP-4 expression was found higher in HGPIN and cancer when compared to non-neoplastic acini. |
Prognosis | For the progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to invasive adenocarcinoma, it is crucial to disrupt the continuity of the basal cell layer and basement membrane. MMP-26 may play an integral role during this conversion and may serve as a marker for earlier diagnoses. |
Oncogenesis | MMP-26, by cleaving basement membrane proteins and activating pro-MMP-9, promotes invasion of human prostate cancer cells. |
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Entity | Squamous cell carcinomas (SCC) |
Note | Squamous cell cancers can be recognized as an uncontrolled wound healing process. MMP-26 expression is present in migrating keratinocytes (KC) of healing wounds compared with normal intact skin cells. Furthermore, expression was not found to be present in proliferating Ki-67-positive KC but co-localized with tumor suppressor p16. MMP-26 was also detected in squamous cell cancer (SCC) grades I and II, but was not present in grade III. In another study, high-grade SCC shows a statistically significant higher expression of MMP-26 and is associated with morphological scores of malignancy. MMP-26 is suggested to contribute to more aggressive behavior of SCCs in organ transplant recipients. In SCC of the esophagus (ESCC), MMP-26 was upregulated in incipient invasion and its expression associated with regions of low differentiation being more sporadic at the invasive front. MMP-26, nuclear β-catenin, and active MMP-9 expression correlate in ESCC tissue, which was found significantly correlated with depth of invasion, lymph node and distant metastasis, advances in pTNM stage, and recurrence. |
Disease | Oral squamous cell carcinomas, Esophageal squamous cell carcinoma. |
Prognosis | Lack of MMP-26 in SCC could be a marker of aggressive growth. Another report questions the usefulness of MMP-26 as an indicator of the metastatic potential of SCCs of the tongue. MMP-26 positive ESCC patients showed significantly shorter overall and disease-free survival periods than those did with MMP-26-negative cancers. |
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Entity | Lung cancer |
Note | Expression of MMP-26 is significantly higher in non-small cell lung cancer (NSCLC) than in atypical hyperplasia and normal lung tissue and correlates with carcinogenesis, lymph node metastasis, clinical stage, and prognosis. Silencing of MMP-26 significantly reduced invasiveness of A549 cells in Transwell invasion assays, suggesting MMP-26 to play an important role in local invasion, at least in part through coordination with MMP-9. |
Disease | Non-small Cell Lung Cancer (NSCLC). |
Prognosis | MMP-26 may be used as a tumor marker in monitoring progression and predicting prognosis of NSCLC since disease-free and overall survival are shorter in NSCLC patients with high expression of MMP-26. |
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Entity | Glioblastoma multiforme (brain tumor) |
Note | Overexpression of MMP-26 in U251 cells resulted in a significantly higher cell-spreading ratio when compared to parental U251 cells. The relative migration distance on Matrigel was also significantly greater. Boyden Chamber assays further indicated an enhanced invasive ability of MMP-26 overexpressed U251 cells. The microvessel density of tumor tissues derived from MMP-26 transfected cells was also greater when compared to the parental cell line. |
Oncogenesis | MMP-26 contributes to U251 cell invasion and migration in vitro and plays an important role in local invasion and angiogenesis. |
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Entity | Merkel cell carcinoma (cutaneous tumor) |
Note | MMP-26 expression was positive in stromal cells and was associated with tumors greater than or equal to 2-cm in diameter. |
Prognosis | Stroma expression is associated with larger tumors with poor prognosis. |
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Entity | Pancreatic cancer, pancreatic adenocarcinoma |
Note | Patients with metastatic cancer cells in lymph nodes had increased expression of MMP-26 in tumor samples. In a pancreatic cell line (PANC-1) MMP-26 was neither expressed basally nor induced by TNF-α, TGFβ1, EGF, or interferon γ. |
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Entity | Colon cancer |
Note | Unlike classical MMPs, MMP-26 is expressed in the normal intestine and was detected in migrating enterocytes. Staining for MMP-26 revealed a meshwork-like pattern between cancer islets and suggested to be involved in enterocyte migration. |
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