Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin (MAM) and maspin are two putative breast tissue-specific markers frequently used for detection of occult tumour cells in the peripheral blood, bone marrow and lymph nodes of breast cancer patients. In this study, it was evaluated whether MAM and maspin gene expression may be induced in the normal blood and bone marrow cells exposed to a panel of cytokines, including chemotactic factors (C5a, interleukin (IL)-8), LPS, proinflammatory cytokines (TNF-alpha, IL-1beta) and growth factors (IL-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor). The experimental data show that all cytokines included in the panel, except for IL-8, were able to induce maspin expression; on the contrary, MAM gene was never induced. These results suggest that MAM is more specific than maspin and that the possible interference of cytokines should be taken into account in interpreting molecular assays for detection of isolated tumour cells.
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PMID:Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer. 1584 Oct 77

The vast majority of invasive breast tumors are ductal and lobular breast carcinomas. Despite the many similarities, some clinical follow-up data and the patterns of metastases suggest that these histological subtypes of breast cancer are biologically distinct. Few papers, however, describe immunohistochemical markers useful for differentiation of these carcinomas. Many investigations suggest that E cadherin protein expression is lost in lobular but not in ductal carcinoma. The absence of E-CD, as a partial loss of epithelial differentiation, may account for the extended spread of lobular carcinoma in situ and the peculiar diffuse invasion mode of invasive lobular carcinoma. Some investigations report the significance of E-CD associated proteins alpha-, beta-, gamma-catenin expression, as well as the usefulness of cytokeratins 5, 6, 8, 7 and thrombospondin in differentiating histological types of breast invasive carcinomas. Several reports have suggested the possibility that invasive ductal and lobular cancers differ with respect to expression of antigens involved in proliferation and cell cycle regulation. It has been shown that vascular endothelial growth factor expression, also the expression of maspin, a tumour suppressor gene product, is higher in ductal, than in lobular carcinoma. Expression of NKX3.1, a member of the NK-class of homeodomain, is highly restricted and is found primarily in lobular carcinoma. Some histological and immunohistochemical characteristics of pleomorphic lobular carcinoma are also discussed.
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PMID:Differentiation of tumours of ductal and lobular origin: I. Proteomics of invasive ductal and lobular breast carcinomas. 1617 Mar 89

For most cancer cell types, the acquisition of metastatic activity leads to clinically incurable disease. Improvements in surgery and radiotherapy, and the development of new chemotherapeutic agents or their use in new combinations, have, so far, only incrementally improved patient survival. Despite the obvious importance of metastasis, the process remains incompletely characterized at the molecular and biochemical levels. Tumor metastasis is a complex process and requires multiple cellular functions over time. From cellular invasion, extravasation from the primary tumor, intravasation to the secondary organs, to successful colonization, tumor cells utilize many cellular or biochemical mechanisms to complete the metastatic spread. During the process of metastasis, there are consistent changes in gene expression. Studies of genes that are reduced or silenced have yielded surprising insights into in vivo mechanisms of regulating tumor metastasis. This review describes a tumor suppressor gene, Maspin, which is often silenced in cancer cells and exhibits suppressing activity against tumor growth and metastasis. Maspin has been shown to be involved in processes that are important to both tumor growth and metastasis such as cell invasion, angiogenesis, and more recently apoptosis. Hence, many efforts have been devoted to deciphering the molecular mechanism of maspin. While some insights have come from the protease inhibitory effect of maspin, more perceptive results on how maspin may function in suppressing tumor metastasis have come from studies of gene manipulation, protein interactions and global protein profiling.
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PMID:Maspin and tumor metastasis. 1654 Apr 29

Maspin is a member of the serpin family of protease inhibitors. It is a 42 kDa cytoplasmic protein that is reported to have tumour suppressor activity. The loss of maspin gene expression is correlated with increased invasiveness and the risk of metastases in breast cancer. We studied maspin expression in primary melanoma lesions obtained from 76 patients. Immunostaining of 5 pm sections for maspin expression was obtained using the citrate antigen retrieval method. The extent of immunostaining was scored by recording the proportion of immunoreactive cells and the intensity of immunostaining. Our results demonstrated that maspin expression was down-regulated in intermediate thickness and thick melanoma lesions compared with thin lesions. These results suggest that loss of maspin expression might play a role in melanoma progression, invasion and metastatic dissemination. Further studies are needed to clarify the clinicopathological significance of maspin expression in melanoma.
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PMID:Decreased immunoreactive maspin expression in intermediate thickness and thick primary melanoma lesions. 1660 23

Maspin, a member of the serpin family of serine protease inhibitors, has been shown to limit invasion and metastases in breast and prostate carcinomas. Maspin gene expression is up-regulated in pancreatic cancer, but not in normal pancreatic tissue. Maspin expression has been documented using immunohistochemical studies in pancreatic adenocarcinoma and high-grade intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic pancreatitis utilizing tissue microarray technology to determine the utility of maspin in differentiating these lesions. Immunohistochemistry was performed on tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24 cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or poorly differentiated using the WHO criteria. The primary antibody used was monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA). Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1 + to 3 + based on intensity. Cases were considered positive if one or more cores demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1 + to 2 +) staining within occasional benign ductal epithelial cells in 29% of cases (7/24). Diffuse and intense (3 +) staining was present in ducts with squamous metaplasia (3 cases). The majority of ducts showed no staining. Ductal adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally more intense staining than cases of chronic pancreatitis. Maspin may be helpful in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous metaplasia is ruled out.
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PMID:Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray based study. 1753 9

Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily of protease inhibitors and it has a role as a tumor suppressor. Maspin has been reported to be important in processes relevant to tumor growth and metastasis such as cell invasion, angiogenesis, and apoptosis. A high expression of maspin was correlated with better rates of survival and absence of nodal metastases in head and neck squamous cell carcinoma. In contrast, some studies have shown that maspin overexpression is correlated with a poor prognosis in pancreatic and ovarian cancers and in lung adenocarcinoma. The aim of this study was an immunohistochemical evaluation of the maspin expression in oral squamous cell carcinoma and thus 89 patients were evaluated. Maspin expression in oral squamous cell carcinoma was significantly associated with the tumor differentiation grade (chi test: P = 0.0318) and the lymph node status (chi test: P < 0.005), but not with the tumor stage (chi test: P = 0.666). Metastatic involvement of lymph nodes was observed more frequently in maspin-negative cases than in tumors with more than 5% of positive cells (P = 0.0024). The present results confirm that maspin expression predicts a better prognosis in oral squamous cell carcinoma and that maspin probably plays a role in tumor progression.
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PMID:Maspin expression in oral squamous cell carcinoma. 1791 78

The vascular endothelial growth factor (VEGF) family, including VEGFA, VEGFC, and VEGFD, plays an essential role in the angiogenesis of both pathologic and nonpathologic conditions. Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits motility, invasion, and angiogenesis. Few studies have compared maspin with VEGF in ovarian carcinoma. Therefore, we investigated the expression and correlation of maspin, VEGFA, VEGFC, and VEGFD with the tumorigenesis of the ovary and clinicopathologic variables. Using immunohistochemistry, we examined maspin, VEGFA, VEGFC, and VEGFD expression in 60 ovarian carcinoma tissues (35 serous papillary carcinomas, 18 endometrioid carcinomas, and 7 primary ovarian mucinous carcinomas). Staining of cells was scored as +2 if more than 50% of the cells were positive, as +1 if less than 50% of the cells were positive, and as negative if none of the cells stained positive. Overexpression of maspin, VEGFC, and VEGFD was significantly associated with high tumor grade (P<.001, P=.004, P<.001, respectively), clinical stage (P=.002, .01, and .001, respectively), the presence of ascites (P<.001, P=.03, and P=.001, respectively), and the presence of metastatic lymph nodes (P=.002, P<.001, and P<.001, respectively). Maspin was correlated with VEGFA (P=.01), VEGFC (P<.001), and VEGFD (P<.001). The VEGFA score was positively correlated with high tumor grade (P=.04), lymphovascular space invasion (LVSI) (P<.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P=.009), maspin, VEGFC (P=.003), and VEGFD (P=.003), but it was not correlated with the presence of ascites and metastatic lymph nodes. Maspin, VEGFC, and VEGFD are expressed in ovarian tumors with a poor prognostic parameters, and seem to play a role in ovarian cancer angiogenesis, progression, and lymph node metastases. Our results indicate that in contrast to most other carcinomas, maspin expression is directly associated with the biological aggressiveness of ovarian carcinoma. These results may offer new insights regarding the role of maspin in ovarian cancer and might also affect the diagnosis and treatment strategies.
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PMID:Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinoma. 1834 98

Maspin is a serine protease inhibitor with anti-tumor activity, including inhibition of tumor growth, angiogenesis, invasion, motility, and metastasis. Normal mammary and prostate cells express maspin at high levels. In contrast, breast and prostate cancer tissue samples and cell lines exhibit reduced or no expression of the maspin transcript. Previously we have demonstrated that introduction of an intact chromosome 18 into the bone-derived metastatic prostate cancer cell line, PC-3, resulted in reduced in vitro growth and in vivo metastatic potential. The goal of this study was to determine whether maspin is the tumor/metastasis suppressor on chromosome 18 responsible for this phenotype. To investigate whether maspin, when produced at endogenous levels, is capable of inhibiting metastasis to bone we transfected a bacterial artificial chromosome (BAC) genomic clone containing the maspin gene into PC-3 cells that aggressively metastasize to bone in an animal model. The BAC transfected PC-3 cells exhibited an in vitro phenotype consistent with maspin acting as a tumor suppressor. Analysis of the PC-3 maspin transfectants in an in vivo bone metastasis assay resulted in significant reduction of the number and severity of skeletal metastasis, compared with parental PC-3 cells. However, maspin had no effect on the ability of PC-3 cells to metastasize to extra-skeletal sites in this model. These results indicate that maspin expression likely plays a role in reducing the tumor cell's ability to seed to bone or in inhibition of growth in the bone microenvironment. However, it does not affect the ability to metastasize to distant sites.
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PMID:Maspin reduces prostate cancer metastasis to bone. 1836 29

Maspin is a serine protease inhibitor belonging to the serpin family, and is known as a tumor-suppressor protein. Maspin also exhibits an inhibitor effect on angiogenesis. Cell adhesion molecules such as E- and P-selectin are known to play an important role in the metastasis mechanism. We evaluated the expression of maspin, E- and P-selectin in 74 papillary thyroid carcinomas, 19 of which had lymph node metastases, and statistically analyzed the relationship between these three proteins and their relation with prognostic factors. Positive correlations were found for maspin positivity and lymph node metastases; thyroid capsule invasion and perithyroidal soft tissue invasion; E-selectin positivity and lymph node metastases, lymphovascular invasion and perithyroidal soft tissue invasion; and P-selectin positivity and lymph node metastases and lymphovascular invasion (p < 0.05). Statistically significant correlations were also found between maspin, E- and P-selectin expressions with each other and with tumor stage (p < 0.05). Inactive cytoplasmic maspin cannot act as a tumor suppressor. Expression of E- and P-selectins in tumor cells facilitates the occurrence of metastases, lymphovascular invasion, and perithyroidal soft tissue invasion. Further studies, in particular molecular investigations, are needed to reveal the detailed interactions between maspin, E-selectin, and P-selectin expression.
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PMID:Maspin, E-selectin, and P-selectin expressions in papillary thyroid carcinomas and their correlation with prognostic parameters. 1859 52

Maspin is a serine protease inhibitor with tumor suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Maspin also modulates apoptosis of tumor cells, possibly by modulating the expression of the B-cell lymphoma-2 family member. p53 regulates the expression of the tumor suppressor gene maspin. Breast cancer is known for its propensity to recur even after decades. The biology behind this phenomenon of tumor dormancy is poorly understood. This study was conducted to clarify the role of maspin and B-cell lymphoma-2 in early and late recurring breast cancer. The expression of maspin, B-cell lymphoma-2, p53, and estrogen receptor was studied by immunohistochemistry in 73 primary breast cancers and in their metastatic relapses detected within 2 years, or 5 or 10 years after primary surgery. The cytoplasmic expression of maspin was significantly higher in the primary tumors of the early metastasizing breast cancers (first tumor relapse within 2 years) and also in their metastases compared to late metastasizing cancers. An opposite activity was observed in the expression of B-cell lymphoma-2. The level of B-cell lymphoma-2 staining was lower in the early relapsing cancers and significantly lower in their metastases, compared to tumors which metastasized 5 or 10 years after primary surgery. High cytoplasmic expression of maspin and low expression of B-cell lymphoma-2 in primary breast cancer predict early tumor relapse.
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PMID:High expression of maspin is associated with early tumor relapse in breast cancer. 1942 67


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