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)

Tubulolobular carcinoma is a type of mammary carcinoma that displays an admixture of invasive tubules and lobular-like cells. Previous reports have shown it to share clinical similarities to lobular carcinoma, whereas more recent studies have shown it to be E-cadherin positive. The aim of the current study was to further explore the immunophenotype of tubulolobular carcinoma, and to document its natural behavior. Nineteen cases of tubulolobular carcinoma and 10 cases each of tubular and lobular carcinoma were retrieved for comparison analysis. Immunohistochemistry was performed with antibodies against estrogen receptor, progesterone receptor, HER2/neu, 34betaE12, E-cadherin, and the catenins. Twenty-five percent of patients with tubulolobular carcinoma presented with greater than stage I disease, compared to 0 and 60% of patients with tubular and lobular carcinoma, respectively. Two patients with tubulolobular carcinoma had tumor recurrence, one of whom also developed metastasis. The majority of all carcinomas were estrogen and progesterone receptor positive. E-cadherin displayed membranous staining in all tubular and tubulolobular carcinomas, and was negative in all lobular carcinomas. Half of each carcinoma subtype displayed granular cytoplasmic 34betaE12 immunoreactivity. alpha-Catenin exhibited partial or complete membranous staining in all tubulolobular and tubular carcinomas, and was negative in all lobular carcinomas. beta-Catenin displayed membranous staining in tubulolobular and tubular carcinomas, whereas all lobular carcinomas had coarse cytoplasmic immunoreactivity. p120 and gamma-catenin displayed membranous staining in 100% of tubulolobular and tubular carcinomas and cytoplasmic staining in 100% of lobular carcinomas. Tubulolobular carcinoma of the breast is thus a distinct type of mammary carcinoma that displays both tubular and lobular patterns histologically but displays the membranous E-cadherin/catenin complex characteristic of the ductal immunophenotype. Tubulolobular carcinoma appears to be more aggressive than tubular carcinoma, as 16% of patients had lymph node metastases, although all were alive at a mean follow-up of 40 months.
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PMID:The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study. 1865 93

Prolactinoma is the most common pituitary tumour in adults. Macroprolactinomas, particularly in men, may occasionally exhibit a very aggressive clinical course as evidenced by progressive growth, invasion through bone into the sphenoid sinus, cavernous sinus, suprasellar region or the nasopharynx. Some may even progress to pituitary carcinoma with craniospinal or systemic metastases. Aggressive tumours have low cure rates despite appropriate medical and surgical treatment. The mechanisms underlying this aggressive biological behaviour have not yet been fully clarified. Recent immunohistochemical, molecular and genetic studies have provided some insight in this respect. Invasive prolactinomas may be associated with a high Ki-67/MIB-1 labelling index indicating increased cell proliferation, although this is not a universal finding. The AA polymorphism in the cyclin adenine (A)/guanine (G) gene is more frequently detected in invasive prolactinomas. Increased expression of the polysialylated neural cell adhesion molecule (NCAM) and reduced expression of the E-cadherin/catenin complex implies a contribution of altered cell-to-cell adhesion and cellular migration. Extracellular matrix components (ECM), matrix metalloproteinases (MMPs) and their inhibitors play important roles in the context of angiogenesis and invasion. The induction of fibroblast growth factor and vascular endothelial growth factor via oestrogen-induced overexpression of novel genes (PTTG, hst and Edpm5) enhance cell growth, proliferation and angiogenesis contributing to invasiveness in prolactinomas. Although mutations in proto-oncogenes like Ras are uncommon, loss of tumour suppressor genes at loci 11q13, 13q12-14, 10q and 1p seem to be associated with invasiveness. Of the described mechanisms, only reduced E-cadherin/catenin expression and overexpression of hst gene seem to be relatively specific markers for prolactinoma invasiveness compared with other pituitary adenomas. Further research is needed to clarify the molecular mechanisms behind the aggressive course of some prolactinomas to predict those with a potentially poor clinical outcome, and to devise treatments that will eventually enable the cure of these challenging tumours.
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PMID:What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. 1728 3

The sentinel node (SN) technique has gained a key role in breast cancer surgery, allowing for an accurate staging of the axillary status with a minimally invasive resection. In this study, we explored the implication of three proteins (E-cadherin, a- and b-catenins) that form the cadherin-catenin complex, a receptorial structure strictly involved in tumoral vascular invasion and embolization in this biologic event. We studied the immunohistochemical expression of the complex in patients with metastatic SN, matching the group with involved nonsentinel lymph nodes (NSNs) with that having free axillary NSNs. The simultaneous staining of the SN metastases for the three proteins has been considered an indicator of preserved function. Our data confirmed the lack of cadherin-catenin complex in tumors with lobular morphology even in SN metastasis, but statistical evaluation could not prove a significant relation between complex integrity and NSN involvement. Moreover, considering traditional histopathologic parameters, only vascular peritumoral embolization was related to an increased risk of metastatic spread to axillary NSNs.
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PMID:Expression of the E-cadherin-catenins complex in sentinel node is related to tumor morphology but not to spread to nonsentinel nodes. 1757 40

Desmocollin 3 (Dsc3) and desmoglein 3 (Dsg3) are both transmembrane glycoproteins that belong to the cadherin family of calcium-dependent cell adhesion molecules. beta-Catenin is a member of the cadherin-catenin complex that mediates homotypic cell-cell adhesion and is also an important molecule in the wnt signaling pathway. In this study, we examined the simultaneous expression level of Dsc3, Dsg3, and beta-catenin in oral squamous cell carcinomas (OSCCs) and normal oral epithelia using immunohistochemistry. There was a significant correlation (p < 0.05) among the following variables in OSCCs: reduced or loss of expression of Dsc3, Dsg3, and beta-catenin compared to normal oral epithelium, reduced or loss of expression of Dsc3 and histological grade (moderately or poorly differentiated), and reduced or loss of expression of beta-catenin and lymph node metastasis. Furthermore, a positive correlation was found between reduced or loss of beta-catenin staining and reduced or loss of Dsc3 staining in lymph node metastatic cancer tissue (r = 0.734, p < 0.05). These results suggest an abnormal expression of Dsc3, Dsg3, and beta-catenin induced in the progression of oral carcinomas and that the Dsc3 expression level might be related to the regulation of beta-catenin in lymph node metastasis and cell proliferation in OSCCs.
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PMID:Altered expression of desmocollin 3, desmoglein 3, and beta-catenin in oral squamous cell carcinoma: correlation with lymph node metastasis and cell proliferation. 1784 85

Osteopontin is a secreted phosphoprotein that has been implicated as an important mediator of tumor metastasis and has been investigated for use as a biomarker for advanced disease and as a potential therapeutic target in the regulation of cancer metastasis. The OPN DNA sequence is highly conserved and the protein contains several important functional domains including alpha(v)beta integrin and CD44 binding sites. High levels of OPN expression correlate with tumor invasion, progression or metastasis in multiple cancer. Studies demonstrate that osteopontin mediates the molecular mechanisms which determine metastatic spread, such as prevention of apoptosis, extracellular matrix proteolysis and remodeling, cell migration, evasion of host-immune cells and neovascularization. Transcriptional regulation of OPN is complex and involves multiple pathways, including AP-1, Myc, v-Src, Runx/CBF, TGF-B/BMPs/Smad/Hox, and Wnt/ss-catenin/APC/GSK-3ss/Tcf-4. The current state of knowledge of OPN biology suggests that it is an attractive target for therapeutic modulation of metastatic disease.
Cancer Metastasis Rev 2008 Mar
PMID:Osteopontin: regulation in tumor metastasis. 1804 63

The cadherin molecules at adherens junctions have multiple isoforms. Cadherin isoform switching (cadherin switching) occurs during normal developmental processes to allow cell types to segregate from one another. Tumor cells often recapitulate this activity and the result is an aggressive tumor cell that gains the ability to leave the site of the tumor and metastasize. At present, we understand some of the mechanisms that promote cadherin switching and some of the pathways downstream of this process that influence cell behavior. Specific cadherin family members influence growth-factor-receptor signaling and Rho GTPases to promote cell motility and invasion. In addition, p120-catenin probably plays multiple roles in cadherin switching, regulating Rho GTPases and stabilizing cadherins.
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PMID:Cadherin switching. 1832 69

Ovarian cancer takes a fourth place as cause of death from all cancers and a first place from gynecologic malignancies in Poland. Up to now, relatively little is known about immunohistochemical markers accepted as prognostic indicators for ovarian cancers. Recent investigations took a note of prognostic significance of catenin-cadherin adhesion complex and Ki-67 proliferation protein in serous ovarian cancers. The aim of the study was to evaluate the immunoexpression of beta-catenin and E-cadherin in metastatic and nonmetastatic serous ovarian tumors, as well as to find possible relationships between this immunoexpression and tumor proliferation activity. The analysis comprised of 66 women diagnosed and treated for epithelial ovarian tumors. On immunohistochemical examinations it was found a significantly lower immunoexpression of beta-catenin and E-cadherin in invasive serous ovarian cancers than in cystadenomas. Additionally, in metastatic group the immunoexpression of both beta-catenin and E-cadherin was significantly decreased as compared with patients without metastases. Moreover, the significant inverse correlations have been shown between immunoexpression of Ki-67 and beta-catenin as well as Ki-67 and E-cadherin. In conclusion, our data suggest that decreased immunoexpression of beta-catenin and E-cadherin in serous ovarian tumors may be helpful in identifying the cases of higher metastatic potential and infiltration ability.
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PMID:Immunoexpression of beta-catenin--E-cadherin complex in primary serous ovarian tumors. 1865 68

Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy has improved locoregional control, the median survival of approximately 4 months has not changed in more than half a century due to uncontrolled systemic metastases. The objective of this study was to review the literature in order to identify potential new strategies for treating this highly lethal cancer. PubMed searches were the principal source of articles reviewed. The molecular pathogenesis of ATC includes mutations in BRAF, RAS, catenin (cadherin-associated protein), beta 1, PIK3CA, TP53, AXIN1, PTEN, and APC genes, and chromosomal abnormalities are common. Several microarray studies have identified genes and pathways preferentially affected, and dysregulated microRNA profiles differ from differentiated thyroid cancers. Numerous proteins involving transcription factors, signaling pathways, mitosis, proliferation, cell cycle, apoptosis, adhesion, migration, epigenetics, and protein degradation are affected. A variety of agents have been successful in controlling ATC cell growth both in vitro and in nude mice xenografts. While many of these new compounds are in cancer clinical trials, there are few studies being conducted in ATC. With the recent increased knowledge of the many critical genes and proteins affected in ATC, and the extensive array of targeted therapies being developed for cancer patients, there are new opportunities to design clinical trials based upon tumor molecular profiling and preclinical studies of potentially synergistic combinatorial novel therapies.
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PMID:Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. 1898 68

Of all processes involved in tumour progression, local invasion and formation of metastases are the clinically most relevant but the scientifically least well understood at their molecular level. The loss of cell adhesion, then tumour cell migration with changes in the cytoskeleton, invasion and metastatic dissemination are the steps of the "metastatic cascade". The E-cadherin-catenin complex plays a key role in cell adhesion thus building the first step in malignant progression. In many epithelial cancers, E-cadherin is lost concomitantly with tumour progression. Thus beta-catenin dissociates in the cytoplasm and accumulates in the nucleus as a transcription factor. Recent experimental progress has identified that tumour hypoxia not only induces tumour angiogenesis, but also modulates malignant progression to initiate tumour invasion and metastasis. It was hypothesised that hypoxia within tumours causes dysfunction of the E-cadherin-catenin complex with an accumulation of beta-catenin in the nucleus and produces an invasive phenotype of tumour cells. For this purpose fertilized chicken eggs were incubated for ten days in normoxic conditions. Subsequently colon carcinoma cells (SW-480) were placed on the chorioallantoic membrane. During the following six days the eggs were incubated either in normoxic conditions or in stepwise decreasing hypoxic conditions. SW-480 colon carcinoma cells did not invade the epithelial layer in normoxic conditions. beta-catenin was membrane bound or in the cytoplasm. The nuclei were regularly omitted. In contrast, an invasion through the epithelial layer into the mesoderm was already seen after three days when incubated in hypoxic conditions. beta-catenin was membrane bound in non-invasive regions of the tumour nodule but there was an accumulation of beta-catenin in the nucleus in the invasive tumour front. Hypoxia seems to be responsible for accumulation of beta-catenin in the nucleus which is accompanied by a more invasive phenotype of tumour cells at the tumour front.
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PMID:Malignant progression of invasive tumour cells seen in hypoxia present an accumulation of beta-catenin in the nucleus at the tumour front. 1948 39

Prostate cancer is the first most common malignancy in men worldwide; this cancer is characterized by a marked propensity for invasion and spreading to local lymph nodes. On the other hand, Teucrium polium (TP) is a medicinal plant that has been used for more than two thousand years for treating many diseases such as abdominal pain, indigestion and diabetes in the Middle East. However, the effect of TP plant extract on human metastatic cancer cells especially prostate has not been investigated yet. In this study, we examined the effects of TP extract on selected parameters in PC3 and DU145 prostate cancer cell lines. Our results show that TP plant extract inhibits cell proliferation and provokes S cell cycle arrest and reduction of G0-G1 phase. In parallel, this extract induces differentiation to an epithelial phenotype "mesenchymal-epithelial transition" which is an important event in cell invasion and metastasis; thus TP plant extract causes a dramatic decrease in cell invasion and motility abilities of PC3 and DU145 cancer cells in comparison with untreated cells. These changes are accompanied by a re-localization of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of the TP plant extract revealed that it inhibits the phosphorylation of beta-catenin, via Src dephosphorylation, and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that TP plant extract inhibits signaling pathways involved in regulating the E-cadherin/catenin complex and possibly other cell-cell adhesion genes via beta-catenin alteration, suggesting that this plant extract has therapeutic promise in the treatment of human metastatic prostate cancer.
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PMID:Teucrium polium plant extract inhibits cell invasion and motility of human prostate cancer cells via the restoration of the E-cadherin/catenin complex. 1989 22


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