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Results for “carcinoma metastasis pathways”

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At least 19 recordsLinked to original sources
PubMed2005

[Correlation between the activation of AP-1 signal transduction pathway and metastasis of colorectal carcinoma].

OBJECTIVE: To investigate the binding activity of activator protein-1 (AP-1) with DNA probe in the colorectal carcinoma (CRC) tissues and surrounding tissues and explore the correlation between the activation of AP-1 signal transduction pathway and metastasis of CRC. METHODS: The AP-1 DNA binding activities were investigated by electrophoretic mobility shift assay (EMSA) in CRC specimens (T), surrounding tissues including 2 cm (P(2)), 5 cm(P(5)) far away from primary tumor margin and distal resection margin of the specimens (N). The mRNA expression level of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) were measured by quantitive reverse transcription polymerase chain reaction (Q- RT-PCR). RESULTS: The AP-1 DNA binding activity in T was significantly higher than those in P(2), P(5) and N (P< 0.05) tissues. There were significantly positive correlations between AP-1 DNA binding activity in tumor and invasive degree, lymphatic metastasis respectively (P< 0.01), but no correlation with histological classification and differentiation (P> 0.05). The transcription levels of VEGF and MMP-9 in CRC were significantly higher than those in P(5) and N (P< 0.01, P< 0.05) tissues. The transcription levels of VEGF and MMP-9 were significantly correlated with increasing AP-1 DNA binding activity (P< 0.01). CONCLUSIONS: AP-1 is significantly correlated to the invasion and metastasis in CRC. The activation of AP-1 signal transduction pathway might be involved in the angiogenesis and of degradation extracellular matrix during tumor metastasis.

Colorectal Neoplasms↗
PubMed1993

Pathways of nodal metastasis in carcinomas of the cecum, ascending colon, and transverse colon: CT demonstration.

The distribution of regional lymph node metastases in carcinomas of the cecum, ascending colon, and transverse colon follows the vascular distribution in the ileocolic mesentery, ascending mesocolon, and transverse mesocolon. The location of these metastatic nodes can be recognized on CT scans when the anatomy of the vessels in the ileocolic mesentery and mesocolon is well understood. This knowledge is important in the preoperative staging of carcinomas of the colon for curative surgery and in the early detection of recurrent nodal disease after curative surgery.

Cecal Neoplasms↗
PubMed2025

A cell-state axis underlying colonization in carcinomas with implications for metastasis risk prediction and interception.

Metastasis to the liver drives mortality in pancreatic ductal adenocarcinoma (PDAC), yet mechanisms of colonization remain unclear. Using genomic barcoding, we developed a clonal competition model under immune surveillance, isolating murine PDAC subclones with high or low liver-colonization potential. Combined transcriptome and chromatin-accessibility analyses revealed a distinct "metastatic-potential axis," separate from the normal-to-PDAC and classical-basal axes. We established "MetScore" as a biomarker of this axis. MetScore distinguishes metastases from primary PDAC tumors in patients, predicts outcomes beyond classical-basal classifications, and generalizes across carcinoma subtypes, suggesting conserved colonization mechanisms. High-MetScore PDAC cells preferentially occupy immune cell-enriched niches, suggesting they remodel the metastatic microenvironment. Functional screening identified c-Fos as a positive mediator of colonization and a candidate anti-metastatic target. Collectively, we identify a cell-state axis underpinning PDAC liver colonization, introduce MetScore as a broadly applicable biomarker, and nominate actionable targets for peri-operative therapeutic intervention.

Animals↗
PubMed2004

Syngeneic lymph-node-targeting model of green fluorescent protein-expressing Lewis lung carcinoma.

The Lewis lung tumor has been extensively studied in both syngeneic and allogeneic mouse models. However, its metastatic potential and mechanism are poorly understood. The aim of the present study was to develop a highly metastatic lymph-node targeting, imageable model of the Lewis lung carcinoma in a syngeneic host. We report here a syngeneic model of the Lewis lung carcinoma in which the carcinoma cells are labeled with green fluorescent protein (GFP). The tumor cells were transplanted in the dorsal side of the ear of C57-B16 mice in order to give the tumor cells access to the lymphatic system. This model of the Lewis lung carcinoma extensively metastasized to numerous lymph nodes throughout the body of the animal as well as visceral organs, as visualized by fluorescence microscopy using the bright GFP signal. Twenty-one different metastatic sites, including lymph nodes throughout the body, were identified among the cohort of transplanted animals. The data demonstrate a predilection of the Lewis lung carcinoma for lymphatic pathways for metastasis throughout the animal body. The concomitant macrometastases to the visceral organs observed in this model may be remetastasis from the lymph nodes. This model of the Lewis lung carcinoma should be very useful in defining cellular trafficking and targeting mechanisms of metastasis, in particular those involving lymphatic pathways.

Animals↗
PubMed1998

Initial presentation of hepatocellular carcinoma as a mandibular mass: case report and review of the literature.

Hepatocellular carcinoma metastatic to the oral cavity is a rare phenomenon. From 1957 to date, 51 case have been documented in the English literature. In this report we describe a case of metastatic hepatocellular carcinoma manifesting itself as unilateral mandibular paresthesia before the discovery of the primary tumor. In addition, we review the literature related to metastatic hepatocellular carcinoma and the pathways of metastasis.

Aged↗
PubMed2003

Recent insights into angiogenesis, apoptosis, invasion, and metastasis in colorectal carcinoma.

The numerous studies profiling mechanisms in colorectal carcinoma have implicated multiple pathways in the malignant progression of a colorectal epithelial cell. Such pathways as aberrations in the cell cycle, deviation from apoptosis, neovascularization of tumors, and invasion and metastasis of malignant epithelial cells have been shown to occur in the progression of a normal epithelial cell to an adenoma and carcinoma. Today, we continue to search for communications or connections between these pathways as we try to get a more global picture of the events responsible for the adenoma-carcinoma sequence. This review focuses on the latest developments of three well-characterized pathways implicated in colorectal carcinoma: angiogenesis, apoptosis, and invasion and metastasis. We will attempt to highlight clinical correlates, when available, with some of the more interesting molecules.

Apoptosis↗
PubMed2005

AKT activation promotes metastasis in a mouse model of follicular thyroid carcinoma.

The phosphatidylinositol 3-kinase/AKT pathway is crucial to many cell functions, and its dysregulation in tumors is a common finding. The molecular basis of follicular thyroid cancer metastasis is not well understood but may also be influenced by AKT activation. We previously created a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta gene (TRbetaPV mouse) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. In this study, we investigated whether our mouse model exhibits similar AKT activation as human follicular thyroid cancer. Western blot analysis on thyroids from both wild-type and TRbeta(PV/PV) mice revealed elevation of activated AKT in TRbeta(PV/PV) mice. Immunohistochemistry and confocal microscopy reveal activated AKT in both the thyroid and metastatic lesions of TRbeta(PV/PV) mice. Whereas all three AKT isoforms were overexpressed in primary tumors from TRbeta(PV/PV) mice in the cytoplasm of thyroid cancer cells, only AKT1 was also found in the nucleus, matching the localization of activated AKT in a pattern similar to human follicular thyroid cancer. In the metastases, all AKT isoforms correlated with phosphorylated AKT nuclear localization. We created primary thyroid cell lines derived from TRbeta(PV/PV) mice and found reduction of phosphorylated AKT levels or AKT downstream targets diminishes cell motility. Activated AKT is common to both human and mouse follicular thyroid cancer and is correlated with increased cell motility in vitro and metastasis in vivo. Thus, TRbeta(PV/PV) mice could be used to further dissect the detailed pathways underlying the progression and metastasis of follicular thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed2003

Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray.

Most colorectal carcinomas (CRCs) arise from adenomas through an archetypal pathogenic pathway, the adenoma-carcinoma-metastasis sequence. Aberrant expression of beta-catenin, p16, E-cadherin and c-myc appears to have played important roles in the development and/or progression of CRC, but their precise distribution pattern and associations in different pathologic loci along CRC's pathogenic pathway have not been thoroughly examined. In this study, a tissue microarray (TMA) containing 85 advanced CRCs in different Dukes stages was constructed. In each of 85 cases, tissue specimens from normal mucosa and primary carcinomas in different layers of the bowel wall were included in the TMA. Tissue specimens from matched adenoma, lymph node metastases and distant metastases were obtained from 22, 21 and 21 cases, respectively. Expression patterns of beta-catenin, p16, E-cadherin and c-myc were evaluated by immunohistochemistry. The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05). These results suggest an association between nuclear overexpression of beta-catenin and/or p16 and CRC lymph node metastasis but not distant metastasis. The results also showed that correlative high nuclear expression of beta-catenin and c-myc was observed in primary carcinomas involving the serosa and lymph node metastases (p < 0.05) but not in other pathologic regions of CRCs, suggesting that the tumor microenvironment in different pathologic loci of colorectal tumorigenesis and progression may influence c-myc responsiveness to beta-catenin/Tcf activation.

Colorectal Neoplasms↗
PubMed1995

Axillary lymph node metastases of bronchogenic carcinoma.

BACKGROUND: Metastasis of bronchogenic carcinoma to axillary lymph nodes is rare. The pathways and possible significance of axillary lymph node metastasis from bronchogenic carcinoma were investigated. METHODS: Seventeen patients with probable axillary lymph node metastases from bronchogenic carcinoma were identified by computed tomography. There were 15 nonsmall cell lung cancers and 2 small cell lung cancers. Axillary lymph node metastasis was proven by biopsy in six cases. Metastases were presumed because of an increase in the size of axillary lymph nodes compared with prior studies in six patients and enlarged axillary lymph nodes associated with biopsy-proven ipsilateral supraclavicular lymph node metastasis in five patients. RESULTS: Four of 10 right-sided lung cancers had ipsilateral and six had contralateral axillary lymph node metastases. Six of seven left-sided cancers had ipsilateral and one had contralateral axillary lymph node metastases. Patients with ipsilateral lymph node disease had chest wall involvement and/or supraclavicular and mediastinal lymph node metastases. All seven patients with contralateral axillary lymph node metastases had supraclavicular and/or mediastinal lymph node metastases. CONCLUSION: Bronchogenic carcinoma may involve ipsilateral axillary lymph nodes via either chest wall invasion or retrograde spread from supraclavicular lymph nodes. Contralateral axillary lymph node involvement requires involvement of contralateral mediastinal and supraclavicular lymph nodes with retrograde spread to the axillary lymph nodes.

Axilla↗
PubMed2000

[Inhibition of growth and metastasis of human giant cell carcinoma of the lung by transfection of antisense VEGF121 cDNA].

OBJECTIVE: To explore the effects of blocking the VEGF/VEGF receptor paracrine pathway on growth and metastasis of human lung carcinoma cell line PG and to evaluate its potential application in gene therapy of cancer. METHODS: The eukaryotic expression vectors bearing either sense-VEGF121 cDNA or antisense-VEGF121 cDNA was constructed and transfected into PG cells. In vitro and in vivo tests such as Northern blotting hybridization, Western blotting immunochemistry analysis, as well as xenografting in nude mice were used to analyze the effect of antisense-VEGF. RESULTS: The transfectants stably expressing antisense VEGF121 were observed to produce markedly reduced 3.3 kb VEGF mRNA and 45 KD, 41 KD, 32KD VEGF proteins. When xenografted s.c. into nude mice, growth and metastasis of the antisense-VEGF transfected cell lines were greatly inhibited when compared with control cells. CONCLUSION: Antisense VEGF gene significantly inhibited tumor growth and metastasis and may provide an experimental example for the development of antiangiogenic gene therapy.

Animals↗
PubMed1999

The back door: venous-mediated metastasis into cervical lymph nodes as an alternative metastatic pathway for oropharyngeal squamous cell carcinoma.

Circulating lymphocytes may home to lymph nodes (LNs) via paracortical postcapillary venules, high-endothelial venules (HEVs) that recognize circulating lymphocytes, enabling them to migrate into nodal cortical/paracortical regions. Our goal was to find any histologic, immunohistochemical, or in vitro evidence to support the hypothesis that squamous cell carcinoma (SCC) may gain access to LNs via an alternative venolymphatic pathway. Slides from 67 neck dissections with SCC were studied. Standard criteria for lymphatic-mediated metastasis were used; criteria for evidence ofvenolymphatic metastasis were tumor nests localized to the paracortical regions, directly contiguous to HEVs but not marginal sinuses. Cases in which LN architecture was obliterated by metastases were excluded. A modified Stamper-Woodruff assay, which assesses HEV binding, incubated cell lines from oral carcinomas and lung adenocarcinomas with fresh frozen LN sections. Double-blinded cell counts were performed by two observers and analyzed by Student's t test. Immunohistochemical examination was undertaken on 19 paraffin-embedded cases with the monoclonal antibody, MoAb CD44v6, to discover whether expression of this adhesion molecule correlated with metastatic pattern. Twenty-nine cases (66%) revealed evidence only for the LN route of metastasis; 4 cases (9%) were classified as venolymphatic metastasis; 11 cases (25%) showed evidence for both pathways. The Stamper-Woodruff assay confirmed that SCC cells preferentially bound to HEV within cervical LN sections more than did adenocarcinoma cells (P = .02). Strong staining to MoAb CD44v6 was seen in 18 (95%) of 19 SCCs with a membranous pattern. Occasionally, CD44v6 highlighted tumor emboli adjacent to HEVs, but no overall correlation could be made between CD44v6 expression and pattern of spread. Tumor metastasis via lymphatic channels is the predominant mode of metastatic spread, but the venolymphatic route is a plausible alternative pathway. The preferential attachment of SCC cells to HEVs supports this theory.

Cell Adhesion↗
PubMed2004

p19Arf suppresses growth, progression, and metastasis of Hras-driven carcinomas through p53-dependent and -independent pathways.

Ectopic expression of oncogenes such as Ras induces expression of p19(Arf), which, in turn, activates p53 and growth arrest. Here, we used a multistage model of squamous cell carcinoma development to investigate the functional interactions between Ras, p19(Arf), and p53 during tumor progression in the mouse. Skin tumors were induced in wild-type, p19(Arf)-deficient, and p53-deficient mice using the DMBA/TPA two-step protocol. Activating mutations in Hras were detected in all papillomas and carcinomas examined, regardless of genotype. Relative to wild-type mice, the growth rate of papillomas was greater in p19(Arf)-deficient mice, and reduced in p53-deficient mice. Malignant conversion of papillomas to squamous cell carcinomas, as well as metastasis to lymph nodes and lungs, was markedly accelerated in both p19 (Arf)- and p53-deficient mice. Thus, p19(Arf) inhibits the growth rate of tumors in a p53-independent manner. Through its regulation of p53, p19(Arf) also suppresses malignant conversion and metastasis. p53 expression was upregulated in papillomas from wild-type but not p19( Arf)-null mice, and p53 mutations were more frequently seen in wild-type than in p19( Arf)-null carcinomas. This indicates that selection for p53 mutations is a direct result of signaling from the initiating oncogenic lesion, Hras, acting through p19(Arf).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2003

CC531s colon carcinoma cells induce apoptosis in rat hepatic endothelial cells by the Fas/FasL-mediated pathway.

The mechanisms involved in colorectal carcinoma with liver metastasis are not well known. Metastasizing colon carcinoma cells express more FasL than primary colon carcinoma cells and cancer cells induce apoptosis in hepatocytes by the Fas/FasL pathway. Therefore, this study focused on Fas/FasL expression and functionality in rat liver sinusoidal endothelial cells (LSECs) and CC531s colon carcinoma cells in vitro and in vivo. RT-PCR and immunochemistry revealed Fas and FasL in LSECs and CC531s, respectively. Functionality of Fas was assessed in vitro by incubation with human recombinant FasL (1-100 ng/ml) with or without enhancer. At concentrations of 10 and 100 ng/ml with enhancer, respectively 21% and 44% of endothelial cells showed signs of apoptosis using Hoechst 33342/propidium iodide staining and electron microscopy. In co-cultures, apoptosis could be detected in endothelial cells neighboring the CC531s and could be inhibited by an antagonistic FasL antibody. Moreover, 18 h after mesenteric injection of CC531s, the sinusoidal endothelium revealed disruption. In conclusion, (i). CC531s cells induce apoptosis in LSECs in vitro by using Fas/FasL; (ii). CC531s cells damage the sinusoidal endothelial lining in vivo; and (iii). this might provide FasL-positive tumor cells a gateway towards the hepatocytes.

Adenocarcinoma↗
PubMed1994

Metastasis from a stage IB cervical adenocarcinoma in a transposed ovary: a case report and review of the literature.

Adenocarcinoma originating in the endocervix may remain occult for many years. This may result in an extension to the uterine isthmus and corpus, with subsequent dissemination along the pathways of spread of uterine carcinoma, including metastasis to the ovaries. The patient described in this report had a bulky stage Ib cervical adenocarcinoma with metastasis in a transposed ovary. The metastasis was noted 6 months following postoperative external pelvic irradiation. The sequence of events strongly suggests that microscopic ovarian disease was present at the time of the original surgery. Other cases have been reported; however, the exact incidence is difficult to determine. The current literature on this subject is reviewed and recommendations are made for evaluation and treatment.

Adenocarcinoma↗
PubMed2002

Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage.

BACKGROUND: Caveolin-1 plays a regulatory role in several signaling pathways. Recently caveolin-1 was identified as a metastasis-related gene in prostate carcinoma. However, the clinical impact of caveolin-1 expression in esophageal carcinoma remains unknown. METHODS: One hundred thirty surgical specimens of esophageal squamous cell carcinoma were immunohistochemically assessed for caveolin-1 expression by polyclonal antibody. Caveolin-1 immunoreactivity was correlated with patients' clinicopathologic parameters and outcome. RESULTS: Positive caveolin-1 immunostaining was detected in 58 patients (44.6%). Positive caveolin-1 immunostaining correlated positively with pathologic stage (P = 0.029), pN (P = 0.023), and pM (P = 0.018). The overall survival rate was worse in patients with caveolin-1-positive tumors than in patients with caveolin-1-negative tumors (P = 0.0215). Univariate analyses identified caveolin-1 positivity (P = 0.0238), pT (P = 0.0002), pN (P < 0.0001), pM (P = 0.0002), lymphatic invasion (P = 0.0021), and positive surgical margin (P < 0.0001) as negative prognostic predictors. Multivariate analyses indicated that pT (P = 0.0296), pN (P = 0.0003), and a positive surgical margin (P = 0.0452) were independent prognostic factors. CONCLUSIONS: Over-expression of caveolin-1 is associated with lymph node metastasis and a worse prognosis after surgery in esophageal squamous cell carcinoma.

Adult↗
PubMed1994

Rho small G protein and cytoskeletal control.

The Rho family belongs to the Ras-related small GTP-binding protein (G protein) superfamily and regulates various cell functions in which the actomyosin system is involved, including cell morphology, membrane ruffling, cell motility, cell aggregation, cytokinesis, smooth muscle contraction, and yeast budding. Three GDP/GTP exchange proteins (GEPs), named Smg GDS, Dbl, and Rho GDI, and two GTPase activating proteins (GAPs), named Rho GAP and p190 associated with Ras GAP, have been identified. The Rho activity is likely to be regulated by protein kinase C which is linked through phospholipase C to the tyrosine kinase-type membrane receptors and the heterotrimeric G protein-linked receptors. It is likely that both Ras and Rho receive signals from the membrane receptors through different pathways and transduce signals to genes and cytoskeleton, respectively. In carcinogenesis, mutational activation of any component in the Ras signaling pathway may cause abnormal cell proliferation, whereas mutational activation of any component in the Rho signaling pathway may cause invasiveness and metastasis of carcinoma cells.

Actomyosin↗