Maspin is a marker for early recurrence in primary stage III and IV colorectal cancer

Snoeren, Nikol; Emmink, Benjamin L.; Koerkamp, Marian J G; Hooff, Sander R. van; Goos, Jeroen; Houdt, Winan J. van; Wit, Meike de; Prins, A.M.; Piersma, S.R.; Pham, T.V.; Belt, Eric; Bril, Herman; Stockmann, H. B. A. C.; Meijer, Gerrit A.; Hillegersberg, Richard van; Holstege, Frank C.P.; Jiménez, Connie R.; Fijneman, Remond J.A.; Kranenburg, Onno; Rinkes, Inne H.M. Borel

doi:10.1038/bjc.2013.489

Cited by 38 publications

(49 citation statements)

References 39 publications

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“…f Average quantification of the wound closure in two independent experiments performed Arch Dermatol Res cancer cells [25]. However, Maspin protein has also been linked with recurrence and metastatic risk in breast [38,51], colorectal [39] and bladder cancer [2], and elevated Maspin levels correlates with good prognosis in esophageal [45] and oral SCC [47]. Moreover, a decreased expression of Maspin has recently been demonstrated to correlate with an increased malignancy of mouse and human tumor epidermal cells [4,5].…”

Section: Discussionmentioning

confidence: 99%

Active nuclear IKK correlates with metastatic risk in cutaneous squamous cell carcinoma

et al. 2015

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About 5% of all cutaneous squamous cell carcinomas (cSCCs) metastasize, which is the principal cause of death by this type of cancer. However, to date there are no reliable biomarkers that categorize those SCC patients that will progress to metastasis. Nuclear active IKKα diminishes Maspin levels in prostate cancer facilitating its metastatic potential. In this paper, we describe the immunohistochemical analysis of active IKK and Maspin in 56 metastasizing and 51 non-metastasizing primary cSCC to measure their association with cancer behaviour. We also determined the effect of inhibiting IKK activity in SCC cell growth and migration in vitro. We found that high levels of nuclear active IKK in the primary tumour are predictive of cSCC metastatic capacity, in particular when combined with poor tumour differentiation and a history of tumour recurrence. Active IKK inversely correlated with Maspin levels in cSCC tumours, and samples negative for Maspin are exclusively found in the metastatic group. Mechanistically, IKK activity regulates cellular motility and SCC cell survival. Our results indicate that nuclear active IKK is a robust biomarker to predict cSCC outcome, and suggest the possibility of targeting IKK activity as a future therapy for treating metastatic cSCC.

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Section: Discussionmentioning

confidence: 99%

Active nuclear IKK correlates with metastatic risk in cutaneous squamous cell carcinoma

et al. 2015

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“…Maspin can inhibit serine protease, and several studies have demonstrated that maspin can inhibit tumor growth by inducing apoptosis (14,15). In certain types of tumor, maspin is often expressed at low levels (16).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of IGFBP-2 improves the sensitivity of bladder cancer cells to cisplatin via upregulating the expression of maspin

Hui

Feng

Shi

et al. 2015

International Journal of Molecular Medicine

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The present study aimed to reveal the association between insulin-like growth factor binding protein-2 (IGFBP-2) and the sensitivity of bladder cancer cells to cisplatin, and determine the underlying mechanism involving maspin. A total of 32 bladder cancer tissue samples were collected for analysis. Cells of the BIU87 human bladder cancer cell line were cultured and a cisplatin-resistant subline (BIU87-CisR) was established by continuous exposure of the cells to cisplatin. Targeted inhibition of IGFBP-2 in the BIU87-CisR cells was performed using small interfering RNA technology. The expression levels of IGFBP-2 and maspin in the tissue samples and cells were analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Cell viability following treatment in each group was evaluated using a Cell Counting Kit-8 assay subsequent to treatment with 3 μM cisplatin. The cell cycle and apoptotic rate of the BIU87-CisR cells were analyzed using flow cytometry. Finally, maspin-overexpressing BIU87-CisR cells were used to confirm the effect of maspin on the sensitivity of the cells to cisplatin. The expression levels of IGFBP-2 in chemoresistant patients and BIU87-CisR cells were significantly increased, compared with those in the chemosensitive patients and BIU87 cells, respectively. However, the expression levels of maspin were lower in the cisplatin-resistant tissue and cells, and was enhanced by IGFBP-2 inhibition. Cisplatin (3 μM) caused marked proliferation inhibition, cell cycle arrest and apoptosis of the BIU87-CisR cells, the effect of which was enhanced by IGFBP-2 silencing. Overexpression of maspin also improved the sensitivity of the BIU87-CisR cells to cisplatin. In conclusion, inhibition of IGFBP-2 improved the sensitivity of bladder cancer cells to cisplatin by elevating the expression of maspin.

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“…Enhanced expression of maspin is correlated with unfavorable prognosis in pancreatic, ovarian and colorectal cancer (8)(9)(10). High maspin expression correlates with an unfavorable outcome in colorectal cancer in stage III and IV, suggesting that maspin may have a stage-specific function possibly associated with cancer cell dissemination and/or metastatic outgrowth (11). The maspin expression in the cytoplasm has recently been reported as an independent unfavorable prognostic indicator of patients with lung adenocarcinoma with tumor size <3 cm (12).…”

Section: Introductionmentioning

confidence: 99%

Different maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines

Zhou

Qin

Zhou

et al. 2015

International Journal of Molecular Medicine

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Abstract. Mammary serine protease inhibitor (maspin) is a tumor suppressor gene that is silenced in the majority of cancer cells during metastatic progression by transcriptional and epigenetic mechanisms. The function of maspin in non-small cell lung cancer cells (NSCLC) has not been clearly defined. In the present study, the expression of maspin in NSCLC cell lines, in particular, the adenocarcinoma cell lines, was heterogeneous. While the expression levels of maspin in PC-9 and H460 cell lines were intact, the expression of maspin in the A549 and SPC-A1 cells was hardly detected. Ectopic expression of maspin in A549 cells carrying the K-ras gene point mutation significantly inhibited cell migration and invasion abilities, which was associated with downregulated expression of matrix metalloproteinase-2 and integrin β1. Ectopic expression of maspin in SPC-A1 cells harboring the wild-type K-ras gene predominantly affected cell growth via targeting the AKT signaling molecules. Maspin functions differently in lung adenocarcinoma cells, possibly due to the varied molecular characteristics. IntroductionLung cancer is a leading cause of cancer mortality worldwide. Lung cancer is generally divided into non-small cell lung cancer cells (NSCLC) and SCLC, in which the NSCLC constitutes 80-85% of lung cancers. The three major NSCLC subtypes are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. NSCLC, which is characterized by slow tumor cell growth and dissemination, is refractory to chemotherapy and chest radiotherapy. Several driven genes have been identified in NSCLC, such as EGFR, c-MET and the ALK-EML4 fusion gene (1). Treatment for lung cancer is mainly based on tumor stage, tumor pathology and molecular pathology. Understanding thoroughly the molecular mechanism underlying the aberrant cellular events driving lung cancer progressions is crucial for developing novel treatments.Mammary serine protease inhibitor (maspin), also known as Serpin B5, was first identified in 1994 (2). Maspin belongs to the serine protease inhibitor superfamily, and is predominantly localized in the cytoplasm, but is also localized in the nucleus and membrane, and is secreted. The exact roles of maspin in cancer are far more complicated than initially thought due to the conflicting experimental and clinical data that have been reported. In prostate cancer, the expression of maspin is frequently absent (3). Overexpression of maspin is considered an independent factor in predicting a favorable prognosis in breast cancer and lung squamous cell cancer (4-6). However, it has been also reported that the increased nuclear maspin expression predicts a favorable prognosis, whereas the enhanced cytoplasmic expression is associated with early-relapsing and unfavorable prognosis in breast cancer (7). Enhanced expression of maspin is correlated with unfavorable prognosis in pancreatic, ovarian and colorectal cancer (8-10). High maspin expression correlates with an unfavorable outcome in colorectal cancer in stage III and IV, suggesting th...

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Maspin is a marker for early recurrence in primary stage III and IV colorectal cancer

Cited by 38 publications

References 39 publications

Active nuclear IKK correlates with metastatic risk in cutaneous squamous cell carcinoma

Active nuclear IKK correlates with metastatic risk in cutaneous squamous cell carcinoma

Inhibition of IGFBP-2 improves the sensitivity of bladder cancer cells to cisplatin via upregulating the expression of maspin

Different maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines

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