Maspin is up‐regulated in premalignant prostate epithelia

Pierson, Christopher R.; McGowen, Richard; Grignon, David J.; Sakr, Wael; Dey, Jyotirmoy; Shen, Sheng

doi:10.1002/pros.10107

Cited by 51 publications

(54 citation statements)

References 16 publications

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“…Secondly, the atypical cells of preneoplastic lesions frequently showed strong staining for maspin. It is interesting to note in this context that an upregulation of maspin expression has been reported to occur prior to the premalignant to malignant transition of prostatic epithelia (Pierson et al, 2002).…”

Section: Discussionmentioning

confidence: 94%

“…However, in contrast to these observations, maspin expression has been strongly correlated with reduced survival in breast cancer patients (Umekita et al, 2002) and shown to be a negative prognostic indicator in ovarian carcinoma (Sood et al, 2002). Interestingly, Pierson et al (2002) have recently suggested that maspin upregulation precedes the critical transition from premalignant lesion to invasive prostate cancer.…”

Section: Introductionmentioning

confidence: 97%

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Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

et al. 2003

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Maspin, SCCA1/2 and hurpin were identified by cDNA microarray analyses as dramatically differentially expressed transcripts in primary non-small cell lung cancer (NSCLC). These sequences are located within a 10-gene serpin cluster on 18q21.3. Using comparative RT-PCR, we have investigated the expression of each of these serpins, including their flanking loci, in an independent NSCLC series. Whereas six of the genes (maspin, SCCA1, SCCA2, hurpin, megsin and pAI-2) were commonly differentially expressed in primary lesions, each significantly more often in squamous cell tumours, maspin was identified as the most frequently overrepresented sequence in both squamous cell carcinoma and adenocarcinoma. Using a well-characterized monoclonal antibody, we have shown strong maspin expression in tumour protein extracts, detected multiple isoforms of the 42 kDa protein and shown that maspin is localized specifically to the tumour cells within neoplastic lesions. In contrast, most cells in non-neoplastic lung tissue appear not to express the gene, with the exception of the multipotent basal epithelial cells that line the bronchial airway. These reserve cells generally show strong predominantly nuclear localization of maspin. Strong nuclear expression of maspin within primary tumour cells is correlated with increased survival (P ¼ 0.05) and a longer remission duration (P ¼ 0.02) in resectable-staged patients. However, within the airways of cancer patients and somewhat in contrast to this observation, such expression was more frequently detected in the superficial cells of preneoplastic over non-neoplastic epithelia (Po0.0001), consistent with a role for the protein in early neoplasia.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 97%

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

et al. 2003

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“…We have shown that maspin inhibits breast tumor cell motility and invasion in vitro (29)(30)(31)(32), and breast tumor growth and metastasis in mouse models (29)(30)(31)(32)(33). In human primary PCs, maspin expression consistently appears to be down-regulated at the critical transition from noninvasive, low-grade disease to highly invasive, high-grade PC (34). Although the proteolytic inhibitory activity of maspin has been a subject of debate (32,35,36), probably because of the variations of the in vitro experimental systems, we have shown that maspin exerts a potent inhibitory effect on PC cells DU145-associated uPA͞uPAR (uPA receptor) (32,36).…”

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confidence: 99%

Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis

Cher

Biliran

Bhagat

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Emerging evidence indicates that tumor-associated proteolytic remodeling of bone matrix may underlie the capacity of tumor cells to colonize and survive in the bone microenvironment. Of particular importance, urokinase-type plasminogen activator (uPA) has been shown to correlate with human prostate cancer (PC) metastasis. The importance of this protease may be related to its ability to initiate a proteolytic cascade, leading to the activation of multiple proteases and growth factors. Previously, we showed that maspin, a serine protease inhibitor, specifically inhibits PC-associated uPA and PC cell invasion and motility in vitro. In this article, we showed that maspin-expressing transfectant cells derived from PC cell line DU145 were inhibited in in vitro extracellular matrix and collagen degradation assays. To test the effect of tumor-associated maspin on PC-induced bone matrix remodeling and tumor growth, we injected the maspin-transfected DU145 cells into human fetal bone fragments, which were previously implanted in immunodeficient mice. These studies showed that maspin expression decreased tumor growth, reduced osteolysis, and decreased angiogenesis. Furthermore, the maspin-expressing tumors contained significant fibrosis and collagen staining, and exhibited a more glandular organization. These data represent evidence that maspin inhibits PC-induced bone matrix remodeling and induces PC glandular redifferentiation. These results support our current working hypothesis that maspin exerts its tumor suppressive role, at least in part, by blocking the pericellular uPA system and suggest that maspin may offer an opportunity to improve therapeutic intervention of bone metastasis.A ndrogen deprivation therapy has been the mainstay of treatment of metastatic prostate cancer (PC) for Ͼ50 years. Usually, this therapy produces tremendous tumor shrinkage and significant clinical improvement. However, the duration of response is limited and disease always recurs. Cytotoxic chemotherapy is commonly added, although this approach offers little chance for meaningful, long-term survival. Thus, new approaches are needed. The skeleton is the major target organ of metastasis in patients with PC, and bone metastasis is associated with poor survival. Can bone-targeted therapy improve survival? In a recent clinical trial (1), a therapeutic, bone-seeking radioisotope was added to standard chemotherapy in patients showing an initial chemotherapeutic response. Survival was prolonged in the patients receiving the bone-seeking radioisotope compared with those receiving chemotherapy alone, suggesting that targeting skeletal metastases is a promising approach in PC treatment.Clinicians have traditionally classified bone metastases as either osteolytic or osteoblastic (2). However, tumor deposits in bone usually contain both bone formation and bone degradation (3-8). A ''vicious cycle'' is created whereby metastatic tumor stimulates bone turnover and bone turnover promotes local tumor growth. To date, various molecules have been implicated ...

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“…[3][4][5][6][7][8] In addition, maspin expression is downregulated in prostate carcinoma cell lines and is frequently absent in primary prostate cancers. [8][9][10][11][12][13] Recent studies showed the regulation of maspin in response to androgen ablation of prostate cancer, which strongly implies that maspin plays a physiological role in growth inhibition 9 and engenders a sensitizing effect on apoptosis. 14 Oral squamous cell carcinomas that are immunopositive for maspin show a longer disease-free interval and overall survival period than tumors negative for maspin.…”

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confidence: 99%

Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix

Quddus

Sung

et al. 2005

Modern Pathology

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Maspin is a serine protease inhibitor with tumor suppression activity. It is expressed in normal breast and prostate tissue but is downregulated or absent in breast and prostate tumors. Recent reports have shown that decreased expression is associated with a greater propensity for metastasis in oral squamous cell carcinomas. We know that some high-grade cervical intraepithelial neoplasia progress to invasive carcinomas while others either persist at the same degree of atypia or regress. The pattern of maspin expression in cervical intraepithelial neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive squamous cell carcinomas of the uterine cervix was studied to determine the relationship between the extent of maspin expression and the progression of cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues. Immunoreactivity was scored semiquantitatively using a scale of 0-3. The sums of the scores of the different groups were compared using the Mann-Whitney U-test. A significant decrease in maspin scores was noted between cervical intraepithelial neoplasia-grade 3 vs invasive squamous cell carcinoma (Po0.005), microinvasive squamous cell carcinoma vs invasive squamous cell carcinoma (Po0.05), and cervical intraepithelial neoplasia-grade 3 vs tumor emboli (Po0.005). Although not statistically significant, scores of cervical intraepithelial neoplasia-grade 3 associated with invasive squamous cell carcinoma were lower compared to that cervical intraepithelial neoplasia-grade 3 without invasive squamous cell carcinoma. These findings suggest that maspin likely plays a role in disease progression from in situ to invasive carcinoma. Virtual absence of maspin immunopositivity in tumor emboli indicates that maspin may also play a role in metastasis. Maspin was identified as a tumor suppressor gene by subtractive hybridization from normal mammary epithelial cells. 1 It is a member of the serine protease inhibitor serpin superfamily and is located at 18q21.3, along with other serpin genes such as squamous cell carcinoma antigens 1 and 2 and PAI-2. 2 Accumulated evidence has demonstrated its role as a tumor suppressor that both inhibits cell motility and enhances the capacity for invasion and metastasis in breast cancer. [3][4][5][6][7][8] In addition, maspin expression is downregulated in prostate carcinoma cell lines and is frequently absent in primary prostate cancers. [8][9][10][11][12][13] Recent studies showed the regulation of maspin in response to androgen ablation of prostate cancer, which strongly implies that maspin plays a physiological role in growth inhibition 9 and engenders a sensitizing effect on apoptosis. 14 Oral squamous cell carcinomas that are immunopositive for maspin show a longer disease-free interval and overall survival per...

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Maspin is up‐regulated in premalignant prostate epithelia

Abstract: An up-regulation of maspin expression precedes, rather than occurs at, the critical transition from premalignant prostate lesion of HGPIN to PC. Our data suggest maspin may mark an important transitional phase and play an important role in the premalignancy of the prostate gland.

Cited by 51 publications

References 16 publications

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis

Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix

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