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

Abstract

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.

Convergence of p53 and Transforming Growth Factor β (TGFβ) Signaling on Activating Expression of the Tumor Suppressor Gene maspin in Mammary Epithelial Cells

“…Consistent with this finding, tissue microarray analyses have shown that Maspin expression is down-regulated in cancers with a high histological grade and low expression correlates with presence of p53 mutations in various tumor types (34). Interestingly, Maspin is overexpressed in lung cancer, suggesting it may have a role other than tumor suppressor (35). p63, a homolog of p53, transactivates the Maspin promoter via directly binding to the p53 site in cancer cells (15).…”

S100A2 is strongly expressed in airway basal cells, preneoplastic bronchial lesions and primary non-small cell lung carcinomas

“…These two subtypes may be delineated by TTF (thyroid transcription factor)-1 expression, which is a lineage marker for peripheral airway cells, including type I and II pneumocytes (Yatabe et al, 2004). Interestingly, TTF-1 expression in adenocarcinoma is inversely correlated with expression of maspin (Kobayashi et al, 2004), which we have previously shown to be tightly restricted to basal cells of the bronchial epithelium in normal lung (Smith et al, 2003). Normal alveoli do not express S100A2.…”

“…Comparative multiplex (cm) RT -PCR was used to compare levels of test gene transcripts between normal lung and tumour samples, as described previously (Heighway et al, 2002;Smith et al, 2003). Briefly, the test gene transcript was coamplified with a nondifferentially expressed control transcript (APPBP2 -KIAA0228) in the same reaction.…”

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

“…It is active in cell transition, invasion and metastasis (7). maspin is largely an intracellular protein that is soluble in the cytoplasm and is also found in association with secretory vesicles (45).…”

“…Thyroid tumors generally express TTF-1 diffusely while immunoreactivity in lung carcinomas is particularly high in SCLCs and ACs in contrast (6). maspin, one of the serine protease inhibitor proteins, leads to reduction in cell permeability, invasion and metastasis (7). It is more commonly expressed in SCCs than in other lung tumors (8).…”