Maspin nuclear localization is linked to favorable morphological features in pulmonary adenocarcinoma

Lonardo, Fulvio; Li, Xiao Hua; Siddiq, Fauzia; Singh, Rajesh; Al-Abbadi, Moussa; Pass, Harvey I.; Shen, Sheng

doi:10.1016/j.lungcan.2005.07.011

Cited by 73 publications

(107 citation statements)

References 40 publications

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“…Alternatively, it is possible that maspin exerts its role in the nucleus at the level of gene or chromatin regulation and thus indirectly affects the cell-matrix interaction or differentiation state. This would be consistent with previous reports of nuclear maspin (47)(48)(49)(50)(51)(52)(53)(54) and the redistribution of maspin from the nucleus to the cytoplasm on MCF10A differentiation shown in this study. It is also consistent with observations that maspin interacts with the transcription factor IRF6 (18) and that a related clade B serpin has chromatin remodeling capability (55).…”

Section: Discussionsupporting

confidence: 94%

Maspin (SERPINB5) Is an Obligate Intracellular Serpin

Teoh

Whisstock

Bird

2010

Journal of Biological Chemistry

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Maspin (SERPINB5) is a tumor suppressor lost in breast and prostate cancer whose molecular function is unknown. It is a non-inhibitory member of the clade B serpins suggested to play a role in a plethora of intracellular and extracellular settings, yet its normal cellular distribution has never been clarified. Here we investigate the distribution of maspin in non-transformed human epithelial cells. By indirect immunofluorescence, maspin has a nucleocytoplasmic distribution in breast (MCF10A) and prostate (RWPE-1) cells and, by immunoblotting and pulse-chase analyses, is neither glycosylated nor secreted. Cell surface biotinylation studies also show that maspin is not present at the cell surface. Differentiation of MCF10A cells into three-dimensional acini results in the redistribution of maspin from the nucleus to the cytoplasm but does not result in secretion. Addition of an efficient conventional signal peptide to maspin directs it into the secretory pathway and results in glycosylation but not secretion. We further show that maspin in the cytoplasm of MCF10A cells is a soluble monomeric protein that is not detectably associated with the cytoskeleton or other extractable components. Taken together, these results suggest that maspin is restricted to an intracellular, possibly nuclear, role in which it influences cell-matrix interactions indirectly. It is probably released only as a consequence of cell damage or necrosis.

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Section: Discussionsupporting

confidence: 94%

Maspin (SERPINB5) Is an Obligate Intracellular Serpin

Teoh

Whisstock

Bird

2010

Journal of Biological Chemistry

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“…Only nuclear, only cytoplasmic, and nuclear and/or cytoplasmic maspin expressions have been compared with the types of tumor in various NSCLC studies (9,45,53). maspin staining is usually nuclear and cytoplasmic in lung SCCs, but nuclear in ACs (50,53,54).…”

Section: Discussionmentioning

confidence: 99%

“…Nuclear positivity is thought to be a good prognostic indicator in lung ACs but cytoplasmic staining has been associated with shorter survival in some studies (49,53,55,56). Sood at al.…”

Section: Discussionmentioning

confidence: 99%

Expression of p63, ttf–1 and maspin in non-small cell lung carcinoma and their effect on the prognosis and differential diagnosis

Yaman¹,

Nart²,

Ekren³

et al. 2015

TJPATH

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Objective: Lung cancer is still the leading cause of cancer mortality. Antiapoptotic genes and protease inhibitors play an important role in the development of lung cancer.Material and Method: p63, TTF-1 and maspin expression and their role in the differential diagnosis, overall survival, progression-free survival and other clinicopathological characteristics of the patients were investigated in 80 surgically-resected non-small cell lung carcinomas. Results:The maximal tumor diameter range was 1.5-11 cm (mean: 4.06±1.8 cm). Forty-five (56.3%) tumors were adenocarcinoma, 23 (28.8%) squamous cell carcinoma, four (5%) large cell carcinoma, six (7.5%) large cell neuroendocrine carcinoma, one (1.2%) sarcomatoid carcinoma while one was (1.2%) both adenocarcinoma and squamous cell carcinoma. The patients with advanced TNm stage and a tumor diameter more than 3 cm had markedly poor survival. Immunohistochemically, p63 staining was present in 87.5% of squamous cell carcinomas, 4.3% of adenocarcinomas, 25% of large cell carcinomas, and 16.7% of large cell neuroendocrine carcinomas. Similarly, maspin was positive in 66.7% of squamous cell carcinomas and 17.4% of adenocarcinomas. The TTF-1 staining rate was higher in adenocarcinomas (84.8%). There was no immunoreactivity in squamous cell carcinomas (p<0.001). We found that p63 and TTF-1 had no significant effect on survival in either tumor group (p>0.05) while maspin has a negative prognostic effect in adenocarcinoma (p=0.048). Conclusion:This study suggests that p63 and TTF-1 are reliable markers in non-small cell lung carcinoma and can be used in differential diagnosis. maspin has been identified as a prognostic marker in adenocarcinoma. However, more studies are required to elucidate the significance of maspin.Key Words: Non-small-cell lung carcinoma, p63, TTF-1, maspin, Prognosis ÖZ Amaç: Akciğer kanseri, kanser ölümlerinin önde gelen nedenlerindendir. Antiapopitotik genler ve proteaz inhibitörleri akciğer kanseri gelişiminde önemli role sahiptir. Gereç ve Yöntem:Seksen opere küçük hücreli dışı akciğer karsinom olgusunda p63, TTF-1 ve maspin ekspresyonunun ayırıcı tanıya olan katkıları, sağkalım ve hastalıksız sağkalım üzerine etkileri ve diğer klinikopatolojik özellikler değerlendirildi. Bulgular:Ameliyat materyallerinde izlenen tümörlerin çapları 1,5-11 cm arasında (ort. 4,06±1,8) olup, 45 (%56,3) adenokarsinom, 23 (%28,8) skuamöz hücreli karsinom, dört (%5) büyük hücreli karsinom, altı (%7,5) büyük hücreli nöroendokrin karsinom, bir (%1,2) sarkomatoid karsinom ve bir (%1,2) adenokarsinom ve skuamöz hücreli karsinom birlikteliğinden oluşmakta idi. İleri TNm evreli ve üç cm' den daha büyük tümör çapı olan olgular daha kötü prognozlu idi. İmmünohistokimyasal incelemede skuamöz hücreli karsinomların %87,5'i, adenokarsinomların %4,3'ü, büyük hücreli karsinomların %25'i ve büyük hücreli nöroendokrin karsinomların %16,7'si p63 ile pozitif boyandı. Benzer olarak maspin de skuamöz hücreli karsinomlarda %66,7 ve adenokarsinomlarda %27,4 oranında pozitifti. TTF-1 ekspre...

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“…Recently, many researchers have reported that the mechanism by which maspin suppresses tumors is through the differences in its subcellular localization rather than through differences in expression (positive and negative) (17)(18)(19). Xia et al (20) and Yasumatsu et al (21) reported that decreased maspin expression in OSCC is associated with an unfavorable clinical outcome due to invasion and lymph node metastasis, which is supported by the results of this study.…”

Section: Discussionmentioning

confidence: 99%