scholarly journals Inactivation of EMILIN-1 by proteolysis and secretion in small extracellular vesicles favors melanoma progression and metastasis.

2021 ◽  
Author(s):  
Ana Amor Lopez ◽  
Marina S Mazariegos ◽  
Alessandra Capuano ◽  
Pilar Ximenez Embun ◽  
Marta Hergueta-Redondo ◽  
...  
Keyword(s):  
Lymph Node ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Human Melanoma ◽  
Primary Tumor Growth ◽  
Primary Tumors ◽  
Node Metastasis ◽  
Metastatic Lesions ◽  
Metastatic Cells ◽  
Tumor Growth And Metastasis

Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not defined completely. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth and metastasis in mouse melanoma models. Finally, analysis in human melanoma samples showed that tumor cells with high levels of EMILIN-1 are reduced in metastatic lesions compared to primary tumors or nevi. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.

scholarly journals Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7406
Author(s):  
Ana Amor López ◽  
Marina S. Mazariegos ◽  
Alessandra Capuano ◽  
Pilar Ximénez-Embún ◽  
Marta Hergueta-Redondo ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cell Viability ◽  
Extracellular Vesicles ◽  
Primary Tumor ◽  
Molecular Mechanisms ◽  
Primary Tumor Growth ◽  
Node Metastasis ◽  
Metastatic Cells ◽  
Tumor Growth And Metastasis

Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.

Methylation profiles of genes in breast cancer luminal HER2-negative primary tumor during regional lymphnode metastasis

2021 ◽  
Vol 67 (1) ◽  
pp. 88-94
Author(s):  
A.M. Krasnyi ◽  
S.V. Kurevlev ◽  
A.A. Sadekova ◽  
T.G. Sefikhanov ◽  
V.V. Kometova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Regional Lymph Node ◽  
Statistical Significance ◽  
Aberrant Methylation ◽  
Primary Tumors ◽  
Node Metastasis ◽  
Lymphnode Metastasis ◽  
Node Metastases

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene — p=0.009 (AUC (95%CI) = 0.76 (0.59−0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6−0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.

scholarly journals Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas

2020 ◽  
Vol 22 (12) ◽  
pp. 2357-2363
Author(s):  
A. Arnold ◽  
S. Daum ◽  
M. von Winterfeld ◽  
E. Berg ◽  
M. Hummel ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Distant Metastasis ◽  
Esophagogastric Junction ◽  
Epithelial Tissue ◽  
Prognostic Impact ◽  
Tumor Subtype ◽  
Primary Tumors ◽  
Node Metastasis ◽  
Therapy Target

Abstract Introduction The tight junction molecule Claudin 18.2 is selectively expressed in healthy and malignant gastric epithelial tissue and is a promising therapy target for high Claudin 18.2 expressing adenocarcinomas of the esophagogastric junction and stomach (AEG/S). Methods This study analyzed the prevalence, characteristics and prognostic impact of Claudin 18.2 expression in primary tumor, lymph node and distant metastasis in a large Caucasian AGE/S cohort with 414 patients. Results Claudin 18.2 was highly expressed in 17.1% of primary tumors, 26.7% of lymph node metastasis and 16.7% of distant metastasis. High Claudin 18.2 expression in lymph node metastasis and primary tumors correlated significantly (p < 0.001). High expression of Claudin 18.2 was neither associated with histomorphogical subtype, or tumor state, nor with overall survival. Conclusion In Caucasian AEG/S patients, 17.1% appeared to be eligible for an anti-Claudin 18.2 therapy. Claudin 18.2 expression itself has no impact on prognosis and is not related to any tumor subtype.

Sentinel lymph node mapping for T1 esophageal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 7-7
Author(s):  
Hiroya Takeuchi ◽  
Hirofumi Kawakubo ◽  
Yoshiro Saikawa ◽  
Tadaki Nakahara ◽  
Tai Omori ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Lymph Node Metastasis ◽  
Standard Procedure ◽  
Gamma Probe ◽  
Early Esophageal Cancer ◽  
Radical Esophagectomy ◽  
Primary Tumors ◽  
Node Metastasis

7 Background: Extended radical esophagectomy with three-field lymph node dissection has been recognized as the standard procedure for thoracic esophageal cancer in Japan, even for clinically T1N0 cases. However, to eliminate the uniform application of the highly invasive surgery, we hypothesized that sentinel lymph node (SLN) mapping would play a key role to obtain individual information and allows modification of the surgical procedure for early esophageal cancer. Methods: We have established radio-guided method to detect SLNs in patient with early esophageal cancer using endoscopic injection of technetium-99m tin colloid. Preoperative lymphoscintigraphy and intra-operative use of hand held gamma probe were reliable to locate the radioactive SLNs. Intra-operative gamma probing was also feasible in thoracoscopic or laparoscopic surgery using a special gamma detector which is introducible from trocar ports. Results: SLN mapping has been performed for 70 patients with clinically N0 and early (pT1) esophageal cancer in our institute since 1999. Detection rate of hot node using our procedure was 94% (66/70). The mean number of sentinel nodes per case was 4.6. Twenty-one of 23 cases (91%) with lymph node metastasis showed positive SLNs. Accuracy of metastatic status based on SLN was 97% (64/66). SLNs widely spread from cervical to abdominal areas. In more than 80% of the cases, at least one SLN was located in the 2nd or 3rd compartment of regional lymph nodes. However, 56 (85%) of 66 patients had no lymph node metastasis or metastasis (+) only in SLNs. Conclusions: Our results suggest that SLN concept for clinically N0 and T1 esophageal cancer could be validated. Theoretically more than 80% of patients with pT1b esophageal cancer may be controlled by local treatments such as surgery and chemoradiotherapy targeting primary tumors plus their SLNs. Individualized selective and modified lymphadenectomy targeted on SLN basins for clinically N0 early esophageal cancer should become feasible and clinically useful as less invasive surgical procedures.

scholarly journals VEGF-C–induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1010-1017 ◽  
Author(s):  
Satoshi Hirakawa ◽  
Lawrence F. Brown ◽  
Shohta Kodama ◽  
Karri Paavonen ◽  
Kari Alitalo ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Metastasis ◽  
Fluorescent Protein ◽  
Sentinel Lymph Nodes ◽  
Primary Tumors ◽  
Metastatic Cells ◽  
Good Target ◽  
Green Fluorescent ◽  
Factor C

Abstract The mechanisms by which tumors metastasize to sentinel and distant lymph nodes, and beyond, are poorly understood. We developed transgenic mice that overexpress vascular endothelial growth factor-C (VEGF-C) and green fluorescent protein specifically in the skin and studied the effects of chemically-induced skin carcinogenesis in this model. We found that in contrast to VEGF-A, VEGF-C does not increase the growth of primary tumors, but instead induces expansion of lymphatic networks within sentinel lymph nodes, even before the onset of metastasis. Once the metastatic cells arrived at the sentinel lymph nodes, the extent of lymphangiogenesis at these sites increased. Of importance, in mice with metastasis-containing sentinel lymph nodes, tumors that expressed VEGF-C were more likely to metastasize to additional organs, such as distal lymph nodes and lungs. No metastases were observed in distant organs in the absence of lymph node metastases. These findings indicate an important role of VEGF-C–induced lymph node lymphangiogenesis in the promotion of cancer metastasis beyond the sentinel lymph nodes. VEGF-C is therefore a good target to slow or even prevent the onset of metastasis.

scholarly journals Prognostic and Risk Factors in Patients with Locally Advanced Cutaneous Squamous Cell Carcinoma of the Trunk and Extremities

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
de Lima Vazquez Vinicius ◽  
Cristovam Scapulatempo ◽  
Natalia Martins Perpetuo ◽  
Faheez Mohamed ◽  
Teóclito Sachetto de Carvalho ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Primary Tumors ◽  
Node Metastasis ◽  
E Cadherin

55 patients with advanced cutaneous squamous cell carcinoma (CSCC) of the trunk and extremities were studied.A Tissue Microarraywas constructed using immunohistochemistry to quantify expression of the HER family, E-cadherins, and podoplanin. Clinical and histopathological factors related to lymph node metastasis and prognosis were also established. Primary tumor positivity was 25.5% for EGFR, 87.3% for HER-3, and 48.1% for HER-4. Metastases were positive for EGFR in 41.7%, for HER-3 in 83.3%, and HER-4 in 43.5%. HER-2 was negative in all samples. Membrane E-cadherin and cytoplasmic E-cadherin were positive in 47.3% and 30.2% of primary tumors and 45.5% and 27.3% of metastases, respectively. Podoplanin was positive in 41.8% of primary tumors and 41.7% of metastases. Intratumoral lymphocytic infiltrate was associated with lymph node metastasis. Patients with T3 tumors had better cancer-specific survival (CSS) than those with T4 tumors; patients with no lymph node involvement had better CSS than patients with N1 tumors. Undifferentiated tumors and hyperexpression of podoplanin were negative prognostic indicators on multivariate analysis.

scholarly journals Intratumor Heterogeneity and Evolution of Colorectal Cancer

2020 ◽  
Author(s):  
Santasree Banerjee ◽  
Xianxiang Zhang ◽  
Shan Kuang ◽  
Jigang Wang ◽  
Lei Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Driver Mutations ◽  
Intratumor Heterogeneity ◽  
Primary Tumors ◽  
Node Metastasis ◽  
Evolution Pattern ◽  
Whole Exome ◽  
Colon And Rectum ◽  
High Depth

AbstractIntratumor heterogeneity (ITH) enable us to understand the evolution of cancer. ITH and evolution of colorectal cancer (CRC) has not been well studied. In this prospective study, we recruited different stages of 68 CRC patients with primary tumor at right-sided colon, left-sided colon and rectum. We performed high-depth whole exome sequencing of 206 multi-region tumor samples including primary tumors, lymph node metastasis (LN) and extranodal tumor deposits (ENTD). Our result showed extreme ITH with Darwinian pattern of CRC evolution, evolution pattern of left-sided CRC was more complex and divergent than right-sided CRC and both LN and ENTD were of polyclonal in origin. Extensive ITH was found in driver mutations in KRAS and PIK3CA genes, suggesting major limitations of single biopsies in clinical diagnosis for the CRC patients. In conclusion, our study showed the Darwinian pattern of CRC evolution with differences in evolution pattern between right-sided and left-sided CRC patients.

scholarly journals Deregulation of VEGFR-2 and PGFR Expression and Microvascular Density in a Triple-Negative Model of Canine Malignant Mammary Tumors with Lymph Node or Lung Metastasis

2018 ◽  
Author(s):  
Denner Santos Anjos ◽  
Aline Fernandes Vital ◽  
Patricia de Faria Lainetti ◽  
Antonio Fernando Leis-Filho ◽  
Fabiola Dalmolin ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lung Metastasis ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Mammary Tumors ◽  
Microvascular Density ◽  
Primary Tumors ◽  
Positive Correlation ◽  
Node Metastasis

Canine mammary tumors (CMT) are the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of VEGFR-2, PDGFR and microvascular density (MVD) in a group of metastatic and nonmetastatic triple-negative CMT and compare the expression based on clinical parameters. Twenty-six female dogs with triple-negative mammary tumors were divided into three groups: nonmetastatic tumors (NMT) (N=11), tumors with lymph node metastasis (LNM) (N=10) and tumors with lung metastasis (LM) (N=5). We observed increased VEGFR-2 expression in LNM compared with NMT and a positive correlation between tumor grade and VEGFR-2 expression. A positive correlation was noted between VEGFR-2 and PDGFR expression. Regarding microvascular density (MVD), we identified a higher number of vessels in primary tumors with lymph node metastasis and lung metastasis compared with tumors with no metastasis. The primary tumors with lung metastasis exhibited an increased MVD compared with carcinoma with lymph node metastasis. Overall, our results suggest a deregulation of VEGFR-2 and PDGFR and high MVD in metastatic tumors, indicating a role for angiogenesis in tumor progression.

scholarly journals Development of a Nomogram Combining Clinical Risk Factors and Dual-Energy Spectral CT Parameters for the Preoperative Prediction of Lymph Node Metastasis in Patients With Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuntai Cao ◽  
Jing Zhang ◽  
Haihua Bao ◽  
Guojin Zhang ◽  
Xiaohong Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Logistic Regression ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Dual Energy ◽  
Arterial Phase ◽  
Clinical Factors ◽  
Primary Tumors ◽  
Node Metastasis ◽  
Preoperative Prediction

ObjectiveThis study aimed to develop a dual-energy spectral computed tomography (DESCT) nomogram that incorporated both clinical factors and DESCT parameters for individual preoperative prediction of lymph node metastasis (LNM) in patients with colorectal cancer (CRC).Material and MethodsWe retrospectively reviewed 167 pathologically confirmed patients with CRC who underwent enhanced DESCT preoperatively, and these patients were categorized into training (n = 117) and validation cohorts (n = 50). The monochromatic CT value, iodine concentration value (IC), and effective atomic number (Eff-Z) of the primary tumors were measured independently in the arterial phase (AP) and venous phase (VP) by two radiologists. DESCT parameters together with clinical factors were input into the prediction model for predicting LNM in patients with CRC. Logistic regression analyses were performed to screen for significant predictors of LNM, and these predictors were presented as an easy-to-use nomogram. The receiver operating characteristic curve and decision curve analysis (DCA) were used to evaluate the clinical usefulness of the nomogram.ResultsThe logistic regression analysis showed that carcinoembryonic antigen, carbohydrate antigen 199, pericolorectal fat invasion, ICAP, ICVP, and Eff-ZVP were independent predictors in the predictive model. Based on these predictors, a quantitative nomogram was developed to predict individual LNM probability. The area under the curve (AUC) values of the nomogram were 0.876 in the training cohort and 0.852 in the validation cohort, respectively. DCA showed that our nomogram has outstanding clinical utility.ConclusionsThis study presents a clinical nomogram that incorporates clinical factors and DESCT parameters and can potentially be used as a clinical tool for individual preoperative prediction of LNM in patients with CRC.

scholarly journals Role of Extracellular Vesicles on Cancer Lymphangiogenesis and Lymph Node Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Linlin Wang ◽  
Ling Li ◽  
Guiquan Zhu
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Extracellular Vesicles ◽  
Poor Prognosis ◽  
Biologically Active ◽  
Node Metastasis ◽  
Tumor Lymphangiogenesis ◽  
Different Types

Lymph node metastasis (LNM) of tumors is an established indicator of poor prognosis in patients. Tumor-associated lymphangiogenesis is a key step in LNM and has gained much attention. However, currently, there is no anti-tumor lymphangiogenesis drug used in clinical practice. Recently, studies on extracellular vesicles (EVs) have shown that different types of cells in the tumor microenvironment can release EVs that encapsulate a variety of molecules, including proteins, nucleic acids, and metabolites. Lymph endothelial cells (LECs) regulate tumor lymphangiogenesis through the uptake of EVs packed with different biologically active contents. In this review, we will discuss the possible mechanisms by which EVs participate in the regulation of tumor-associated lymphangiogenesis and LNM, summarize the potential value of EVs that can be used as biomarkers for the determination of tumor LNM, and indicate the potential anti-tumor lymphangiogenesis therapy.

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