Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung

Kodate, Mantaro; Kasai, Takahiko; Hashimoto, Hiroshi; Yasumoto, Kosei; Iwata, Y.; Manabe, Hideo

doi:10.1111/j.1440-1827.1997.tb04525.x

Cited by 110 publications

(72 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Expression of MMP-2 and MMP-9 is elevated in carcinomas in association with low differentiation grade and accelerated tumour progression in oral carcinoma, 30 lung adenocarcinoma, 31 bladder 32 and ovarian carcinoma 33 and papillary thyroid carcinoma. 34 MMP-2 expression correlates also with advanced disease in neuroblastoma.…”

Section: Mmps In Malignant Transformation and Cancer Progressionmentioning

confidence: 99%

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vihinen

Kähäri

2002

Intl Journal of Cancer

581

484

View full text Add to dashboard Cite

Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumour tissue or serum of patients with advanced cancer and their role as prognostic indicators in cancer is studied. In addition, therapeutic intervention of tumour growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors are in clinical trials in cancer. In this review, we discuss the current view on the feasibility of MMPs as prognostic markers and as targets for therapeutic intervention in cancer.

show abstract

Section: Mmps In Malignant Transformation and Cancer Progressionmentioning

confidence: 99%

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vihinen

Kähäri

2002

Intl Journal of Cancer

581

484

View full text Add to dashboard Cite

show abstract

“…[19][20][21] Earlier studies have reported lower frequencies of MMP2 expression in bronchioloalveolar carcinomas. Kodate et al 19 showed that two of 11 cases (18%) of bronchioloalveolar carcinoma expressed MMP2, and that one of 11 cases expressed MMP9. Kitamura et al 20 reported eight of 48 cases (17%) of lung adenocarcinoma expressed MMP2 in the lepidic growth areas.…”

Section: Discussionmentioning

confidence: 96%

“…22 We anticipated that a bronchioloalveolar carcinoma would have little MMP mRNA and minimal gelatinolytic activity, as reported in earlier immunohistochemical studies. 19,20 Surprisingly, in situ hybridization showed that bronchioloalveolar carcinomas had significant amounts of mRNA for MMP2, MMP9, MT1-MMP, and TIMP2. In four cases of bronchioloalveolar carcinoma, the gelatinolytic activity was sufficient to destroy the basement membrane.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression and localization of mRNAs for matrix metalloproteinases and their inhibitors in mixed bronchioloalveolar carcinomas with invasive components

et al. 2005

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are believed to play an essential role in cancer invasion, although detailed differences between noninvasive and invasive lung carcinomas are still unclear. To elucidate the expression and activity patterns of MMPs in noninvasive and invasive carcinoma of the lung, we performed in situ hybridization and real-time reverse transcription-polymerase chain reaction to detect messenger RNAs (mRNAs) of MMPs and their tissue inhibitors (TIMPs). The basement membrane was evaluated by immunohistochemistry for type IV collagen. Gelatinase activity was examined by zymography and in situ zymography. A total of 14 surgically resected primary pulmonary adenocarcinomas were used for this study. All the tumors were adenocarcinoma mixed bronchioloalveolar carcinomas according to the 1999 WHO classification. MMP and TIMP2 mRNAs were detected by in situ hybridization in all samples, in both noninvasive and invasive carcinoma components. Signals for MMP mRNAs were significantly higher in both noninvasive and invasive carcinomas than in tumor-free lung tissue. However, the differences were small between noninvasive and invasive carcinomas, not only in the amount of mRNA but also in the activity of the MMPs. In most carcinomas, stromal fibroblast-type cells tended to express levels of MMP and TIMP2 mRNAs that were higher than or at least similar to those expressed in epithelial cells. Our data on mixed adenocarcinoma suggest that noninvasive carcinoma areas already express a molecular mechanism involving MMPs similar to that expressed by invasive carcinoma areas. Stromal fibroblast-type cells seem to be the most important source of MMPs, from the earliest event of tumor invasion by pulmonary adenocarcinomas. Modern Pathology (2005) 18, 828-837, advance online publication, 14 January 2005; doi:10.1038/modpathol.3800365Keywords: bronchioloalveolar carcinoma; in situ hybridization; matrix metalloproteinase Matrix metalloproteinase (MMP) is essential in remodeling the extracellular matrix. The degradation of the extracellular matrix and basement membranes by MMPs is believed to be crucial in tumor invasion. 1,2 Tissue inhibitor of metalloproteinases (TIMPs) were initially recognized as inhibitors of MMPs, as the name implies. However, subsequent studies revealed that TIMP2 also plays an important role in the activation of MMP2. A complex of TIMP2 and MT1-MMP is now known to be a receptor and activator of MMP2. 3 MMP1, MMP2, MMP3, MMP7, MMP9, MMP11, MMP13, MT1-MMP, TIMP1, and TIMP2 have been detected in various histological types of lung carcinomas. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] However, previous studies rarely examined noninvasive carcinomas, and little is known about how MMP expression differs in noninvasive and invasive carcinomas. Immunohistochemical detection of MMP2 in bronchioloalveolar carcinomas has produced a great variety of results. The expression frequency of MMP2 in bronchioloalveolar carcinomas has been reported to range from 17 to 96%. [19][20][21] This might be du...

show abstract

“…Expression of these enzymes by cancer cells has been found to be correlated with the malignant potential of various cancers (30 -36). Expression of these enzymes may be responsible for tumor invasion and metastasis of T1 adenocarcinoma of the lung (37). We are currently investigating correlations between expression of these enzymes and BM preservation in the same specimens.…”

Section: Bm Preservationmentioning

confidence: 99%

Detection of Early Invasion on the Basis of Basement Membrane Destruction in Small Adenocarcinomas of the Lung and Its Clinical Implications

et al. 2001

View full text Add to dashboard Cite

To evaluate the correlation between the degree of basement membrane (BM) preservation and clinicopathological characteristics in the replacementgrowth type (lepidic growth type) of small peripheral adenocarcinomas of the lung, the BM components of 72 surgically resected replacementgrowth type adenocarcinomas of the lung, 2 cm or less in diameter, were evaluated immunohistochemically by using a monoclonal antibody to Type IV collagen and polyclonal antibodies to 7S collagen and laminin. The tumors were classified into the following three distinctive histological types according to the condition of the elastic framework: Type I, bronchioloalveolar carcinoma without fibrotic foci; Type II, sclerosing bronchioloalveolar carcinoma without elastic framework destruction; and Type III, sclerosing bronchioloalveolar carcinoma with elastic framework destruction. The BM was well preserved in the area of bronchioloalveolar spread along fully expanded alveoli in all tumor types; however, BM preservation was significantly lost in the areas of collapsed alveoli in Type III tumors. There were no BM component staining reactions in the scarred regions of Type III tumors. In addition, lymph node metastasis was significantly greater in Type III tumors and BM-destroyed tumors. We concluded that the BM was largely destroyed by tumor cell invasion in the scarred region of Type III adenocarcinomas. Type III tumors had discontinuous BMs in the area of collapsed alveoli, indicating that this BM-destructive pattern must be the first step in tumor invasion. Type I and II tumors were concluded to be noninvasive adenocarcinomas, because their BM components were well preserved and they had a good outcome.

show abstract

Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung

Cited by 110 publications

References 37 publications

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Expression and localization of mRNAs for matrix metalloproteinases and their inhibitors in mixed bronchioloalveolar carcinomas with invasive components

Detection of Early Invasion on the Basis of Basement Membrane Destruction in Small Adenocarcinomas of the Lung and Its Clinical Implications

Contact Info

Product

Resources

About